Transcript
Page 1: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

Research ArticleShrinkage of Prostate and Improved Quality of LifeManagement of BPH Patients with Croton membranaceusEthanolic Root Extract

George Awuku Asare1 Daniel Afriyie2 Robert A Ngala3

Alfred A Appiah4 Yvonne Anang13 Iddi Musah2 Samuel Adjei5

Kwabena Bamfo-Quaicoe6 Derick Sule6 Ben A Gyan5

Peter Arhin7 and Dominic A Edoh4

1Department of Medical Laboratory Sciences University of Ghana School of Biomedical and Allied Health SciencesKorle Bu Accra Ghana

2Ghana Police Hospital Cantonment Accra Ghana3Department of Molecular Medicine Kwame Nkrumah University of Science and Technology Kumasi Ghana4Center for Plant Medicine Research Mampong Akuapem Ghana5Noguchi Memorial Institute for Medical Research University of Ghana Accra Ghana6Department of Radiography School of Biomedical and Allied Health Sciences University of Ghana Accra Ghana7Traditional and Alternative Medicine Council Ministry of Health Accra Ghana

Correspondence should be addressed to George Awuku Asare gasarechsedugh

Received 17 December 2014 Revised 13 February 2015 Accepted 23 February 2015

Academic Editor Giuseppe Morgia

Copyright copy 2015 George Awuku Asare et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Benign prostatic hyperplasia (BPH) is an enlargement of the prostate The study aimed at validating the use of freeze-driedCroton membranaceus ethanolic root extract for BPH management Thirty-three patients were observed before and after 3-monthadministration of 20mg tid orally The International Prostate Symptom Score (IPSS) and the International Index of ErectileFunction (IIEF) questionnaires were used Totalfree PSA (tPSA fPSA) renal liver function lipid tests and ultrasonographicimaging were performed Thirty (30) patients (66 plusmn 11 years) completed the study IPSS results showed 37 had severe 40moderate and 23 mild symptoms before 57 and 43 had moderate and mild symptoms respectively after treatment IIEDof patientsrsquo results showed 30 with severe 40 moderate 24 mild-moderate 3 mild and 3 no erectile dysfunction beforetreatment and 20 severe 43 moderate and 37 mild-moderate dysfunction after treatment Quality of life (QoL) improved(119875 = 0001) Significant but non-pathological increases in total and indirect bilirubin as well as apolipoprotein A occurred MeantPSA reduced from 279 plusmn 190 to 162 plusmn 118 ngmL (119875 = 0002) fPSA from 61 plusmn 48 to 39 plusmn 29 ngmL (119875 = 0045) and prostatevolume from 1018 plusmn 413 to 545 plusmn 248 cm3 (119875 = 0023) C membranaceus shrinks the prostate and improves QoL

1 IntroductionBPH is an enlargement of the prostate gland from progres-sive hyperplasia or abnormal growth of cells of glandularepithelial and stromal cells [1 2] Commonly experiencedsymptoms include inability to delay urination incompleteemptying of the bladder frequent urination during the dayand night weak urine stream incontinence and painful orbloody urination [3]

Globally it has been documented that more than 80 ofmen by the age of 80 years will suffer fromBPH [4] AlthoughBPH has a wide variety of treatment options from surgicalto complementary alternative medicine (CAM) the highurologist to patient ratio as well as socioeconomic problemsthat plaque developing economies tend to drive the majorityof the BPH patients towards dependency on CAM as the firstline of medical relief Indeed CAM and the use of medicinal

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 365205 10 pageshttpdxdoiorg1011552015365205

2 Evidence-Based Complementary and Alternative Medicine

plants appear to be increasing worldwide Furthermore mostmen are reluctant to opt for surgical interventions for fearof losing potency and the perception of other adverse sideeffects The use of 5120572-reductase inhibitors and 120572-1 blockersfor BPH management has side effects including erectiledysfunction (ED) [5 6] Against this background subjectssuffering from BPH appreciably resort to CAM with asmuch as 90 of men in Austria and Germany depending onphytotherapy [7]

The role of phytotherapy in the health care deliverysystem is increasing It is estimated that the global marketfor medicinal plants is worth over $250 billion [8] Althoughthe economic data does not exist in Ghana medicinal plantpervoyeurs as well as their clients have increased BPHpatients in Ghana resort to the use of medicinal plants or acombination of medicinal plants and radiotherapy [9]

Traditional pharmacologic therapies although widelyused must be assessed for a favorable risk-benefit ratio Onesuch plant that has been studied over three decades in Ghanais Croton membranaceus Mull Arg (Euphorbiaceae) Thisplant is mostly available in three west African countriesnamely Ghana Nigeria and Niger In Ghana the plant ismostly found in the Krobo-Gyakiti forest reserve area in theEastern Region The root preparation of this medicinal planthas been dispensed to BPH patients at the Center for PlantMedicine Research (aWHOCenter) for the past 30 years [10]

The root extract is said to contain an alkaloid a coumarinditerpenoids and phytosterols [11ndash14] Compounds isolatedfrom the root extract include julocrotine scopoletin DL-threitol crotomembranafuran gomojoside H larixol 120573-sito-sterol 120573-sitosterol-3-O-glucoside stigmasterol and campes-terol Furthermore N[N-(2-methylbutanoyl) glutaminoyl]-2-phenylethylamine has recently been isolated [15] Thecrude ethanol extract of C membranaceus and julocrotinepossess 5-120572-reductase inhibitory activity [11] 5-120572-reductaseinhibitory activity is the underpinning mechanism for theapplication of finasteride for the treatment of BPH BPHtreatment with the aqueous root extract alongside finas-teride demonstrating similar efficacy as finasteride has beenreported in an animal model of BPH [16] Furthermorethe antiproliferative activity of C membranaceus on BPH-1cells has been demonstrated [17] Additionally the cytotoxicactivity of the methanolic extract of C membranaceus rootshas been shown against DLD-1 and MCF-7 cells Finally theaqueous root extract of the plant is nontoxic [18] Howeverno published data exist on its effect on human BPH patientsThis study aimed at observing the socioscientific markers ofBPH patients opting for the use of the ethanolic extract of Cmembranaceus

2 Materials and Methods

21 Plant Extract C membranaceus roots were harvestedfrom the forest area of the Eastern Region of Ghana tominimize the presence of contaminating herbicides and pes-ticidesThe root product was carefully extracted with ethanolaccording to the protocol of Appiah [10] Possible variationof content from batch to batch was averted by bulk harvest

and fingerprinting The extract was carefully checked forputative active ingredients(s) using chemical and biologicalparameters Analyses for lack of contamination by pesticidesherbicides heavy metals microbes and toxins were carriedout as part of the quality control procedures The Centerfor Plant Medicine Research (Mampong-Akuapem) furtherprocessed the freeze-dried extract into capsules (10mg percapsule) under strict quality control procedures with arecommended dose of 2 capsules tid The product has beenregistered with the Food and Drug Authority (FDA) Ghanaas URO 500 after satisfying the FDArsquos requirement

22 Experimental Site Eleven (11) centers nationwide havebeen allowed by the Ministry of Health Ghana to serve well-tested and prepared medicinal plants products alongsideorthodox drugs The Ghana Police Hospital Accra whichwas established in 1970 is a medium-size hospital with 100beds The hospital is currently undergoing expansion into anultramodern 400-bed facility It serves as one of the centerscurrently approved by the Ministry of Health to administermedicinal plant products alongside orthodox medicine Thecenter was therefore selected for this study

23 Patients The study obtained ethical clearance fromthe University of Ghana School of Biomedical and AlliedHealth Sciences with ethics clearance number SAHS-ETSAHSPSMML09AA26A2012-2013 for an observa-tional study to be conducted The study complied with theHelsinki Declaration of 1964 with revision in October 2008Patients opting for the use of the herbal remedy and whowere willing to be part of the study were given informedconsent forms Forms were duly filled and the group formedthe cohort Patients were between the ages of 50 and 72 yearsFurthermore patients came from all walks of life howevermost of them were from the capital city of Ghana Accra withfew from Togo and Nigeria The cohort of 33 patients whoopted for phytomedicine was not on any other medicationfor BPH management Furthermore these patients wereunder medical supervision of the urologist on the protocoldevelopment team Patientswere advised to carefully note anyadverse effects and immediately report such using the hotlineprovided

24 Research Instruments Four main research instrumentswere employed The first was the International ProstateSymptom Score (IPSS) questionnaire followed by the sec-ond the International Index of Erectile Function (IIEF)questionnaire The third research instrument was bloodsampling for routine and special biochemical tests and thelast abdominopelvic ultrasonography Research instrumentswere employed before and after 3 months of treatment

241 IPSSQuestionnaire TheIPSS is constructed on answersto seven questions concerning urinary symptoms and onequestion concerning QoL Each question concerning symp-toms in passing urine allowed the patient to choose 1 outof 6 answers representing increasing severity of a particularsymptomThe answers were assigned points from 0 to 5 with

Evidence-Based Complementary and Alternative Medicine 3

5 signifying worsening symptoms The total score thereforeranged from 0 to 35 (asymptomatic to very symptomatic)Symptoms were graded alongside the following incompleteemptying frequency intermittency urgency weak streamstraining and nocturia These first 7 questions of the IPSSwere identical to the questions appearing on the AmericanUrological Association (AUA) Symptom Index The eighthquestion dealt with the patientrsquos perceived QoL and wasscored 0ndash6 with 6 representing a terrible quality of life Com-puted results were categorized as follows mild (symptomscore less than or equal to 7)moderate (symptom score range8ndash19) and severe (symptom score range 20ndash35)

242 IIEF Questionnaire IIEF was based on the effects oferectile problems on onersquos reproductive health life over thepast 4 weeks The 15-point questionnaire finally categorizedanswers into broad areas of erectile function orgasmicfunction sexual desire intercourse satisfaction and overallsatisfaction Clinical interpretation ranged from the lowestscore (no dysfunction) to the highest (severe dysfunction)

243 Biochemical Assays Five milliliters (5mL) of bloodsamples was obtained from the patients before and aftertreatment for various blood tests as part of the urologistrsquosrequest Blood examinations were of two categories routineexaminations and special examinations

(1) Routine Examinations Renal function test (RFT) liverfunction test (LFT) and the lipid profile were performedRFT was made up of urea creatinine Na+ and K+ LFTcomprised total-direct and indirect bilirubin (TBIL DBILand IND BIL resp) aspartate transaminase (AST) alaninetransaminase (ALT) gamma-glutamyl transferase (GGT)alkaline phosphatase (ALP) total protein (TP) and albumin(ALB) Total cholesterol (TC) triglyceride (TG) high den-sity lipoprotein cholesterol (HDL) low density lipoproteincholesterol (LDL) and apolipoproteins A and B made up thelipid profile LDLwas calculated using Friedewealdrsquos equation([LDL-chol] = [Total chol] minus [HDL-chol] minus ([TG]22)) Allroutine examinations were performed using the Vitros 5 IFSChemistry analyzer (New York USA)

(2) Special Examinations Free and total PSA (fPSA andtPSA resp) were performed using Accu-Bind free andtotal PSA ELISA kits were purchased from Monobind Inc(California USA) The tests were performed according tothe manufacturerrsquos instructions In brief serum samples wereadded alongside standards to a highly specific monoclonalanti-PSA antibody coated onto the surface of wells Afterthe first wash an antibody-HRP enzyme conjugate wasapplied to form a sandwich complex on the well surfaceExcess reagents were washed off followed by the additionof 331015840551015840-tetramethylbenzidine (TMB)hydrogen peroxide(substrate) to react with the HRP After stopping the reactionwith sulfuric acid the final chromogen was then read at450 nm using a microplate reader PSA ratio was calculatedas fPSATPSA in

244 Abdominopelvic Scan The SonoScape Digital ColourDoppler Ultrasound System 551ndash6000 (Shenzhen China)was used Patients were asked to drink approximately 15 Lof water and allowed to wait for 1-2 hours before the scanwas performed The purpose of this preparation was to getthe urinary bladder filled with urine so as to act as anacoustic window through which the prostate could better bevisualized Patients were then positioned on the ultrasoundcouch With the pelvic area exposed a liquid gel was appliedon the probe surface to improve the contact between thepatientrsquos skin and the probe surface The prostate volumeand bladder volume at full capacity were obtained After thescanning procedure patients were then asked to void urineafter which a second scan to determine the postvoid residualvolume of the urinary bladder was performed

25 Statistical Analysis Data for the studywas analyzed usingGraphpad Prisms 601 Studentrsquos t-test for paired data wasperformedDescriptive statisticswas presented asmeanplusmn SDPearsonrsquos correlation analysis was performed to determineassociations

3 Results

31 Demographic Data In all 30 clinically diagnosed BPHpatients attending the urology and phytomedicine clinicswith an average age of 66 plusmn 11 years completed the 3-monthobservational study 3 others were excluded for noncompli-ance No report of adverse effects was registered by any ofthe patients during the study However one diabetic patientreported improved glycemic index which further supportsour unpublished data of possible hypoglycemic effect of Cmembranaceus

32 IPSS IPSS relates to the degree of BPH or prostate cancersymptoms experienced Only BPH patients were used forthe study Thirty-seven percent (37) of the patients hadsevere prostate symptoms 40 moderate symptoms and23mild symptoms before treatment with C membranaceusroot extract Fifty-seven (57) and 43 of the patients hadmoderate and mild symptoms respectively after treatmentHowever there was no patient with severe prostate symptomafter treatment

IPSS improved significantly from 151plusmn87units to 103plusmn47 units signifying improved symptoms The decrease wassignificant (119875 = 0005) Additionally QoL improved andthis was highly significant (119875 = 0001) (Table 1) Overallprostate symptom score indicated that severe symptomsdisappeared after treatment while mild and moderate symp-toms increased (Figure 1) In general 33 of the patientsrecruited for this study were happy about their state of healthbefore treatment while 67 of them were unhappy Aftertreatment 83 were happy about their present state of healthwhile 17 remained unhappy A negative correlation betweenQoL and age was observed after treatment although this wasnot significant (Figure 2) Furthermore total IPSS did notsignificantly depend on age (Figure 3) or tPSA levels (Figures4 and 5)

4 Evidence-Based Complementary and Alternative Medicine

7

12

11

13

17

0

0 2 4 6 8 10 12 14 16 18

TIPSS 2TIPSS 1

Severelysymptomatic

Moderatelysymptomatic

Mildlysymptomatic

Figure 1 A diagram showing the prostate symptom score (IPSS)before and after 3 months of plant extract administration

Age (yrs)0 20 40 60 80 100

0

2

4

6

8

QL before

Qua

lity

of li

fe

QL after

Figure 2 A relationship between age and QoL before (b) and after(a) treatment 119903 (b) = minus0010 119903 (a) = minus0330 and 119875 value (b) = 0956119875 value (a) = 0075

Table 1 Table showing prostate symptom score sexual functionand quality of life in BPH patients after three (3) months of Cmembranaceus ethanolic root extract administration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Age (yrs) 660 plusmn 110Total IPSS 151 plusmn 87 103 plusmn 47 0001lowast

Erectile function 100 plusmn 60 97 plusmn 41 0751Orgasmic function 26 plusmn 25 29 plusmn 24 0620Sexual desire 59 plusmn 25 50 plusmn 21 0053Intercourse satisfaction 38 plusmn 32 46 plusmn 25 0154Overall satisfaction 52 plusmn 36 48 plusmn 29 0598Quality of life 33 plusmn 16 17 plusmn 09 0001lowastlowastSignificance at 95 confidence interval

33 IIED Thirty percent (30) of the patients had severeerectile dysfunction 40 moderate dysfunction 24 mild-moderate dysfunction 3 mild dysfunction and 3 nodysfunction before treatment After treatment 20 of the

Age (yrs)0 20 40 60 80 100

0

10

20

30

Total IPSS before

Tota

l IPS

S

Total IPSS after

Figure 3 A relationship between age and IPSS before (b) and after(a) treatment 119903 (b) = 0005 119903 (a) = 0247 and 119875 value (b) = 0981 119875value (a) = 0189

IPSS before

TPSA

bef

ore

0 10 20 300

50

100

150

Figure 4 A correlation between tPSA and IPSS before treatment119903 = minus0089 119875 value = 0640

patients had severe erectile dysfunction 43 moderateand 37 mild-moderate dysfunction No patient had milddysfunction or no dysfunction after treatment

With regard to orgasmic dysfunction 53 had severeorgasmic dysfunction 27moderate 13mild-moderate 4mild and 3 no dysfunction before treatment After treat-ment 37 had severe orgasmic dysfunction 57 moderate3 mild-moderate 0 mild and 3 no dysfunction

Patients with severe dysfunction in sexual desire formed6 Twenty percent (20) 37 27 and 10 hadmoderatemild-moderate mild and no dysfunction in sexual desirerespectively before treatment compared to 10 severe 27moderate 50 mild-moderate 6 mild and 7 no dys-function after treatment Additionally 40 of the patientshad severe dysfunction 33 moderate 24 mild-moderate3 mild and 0 no dysfunction in intercourse satisfactionbefore treatment After treatment 23 had severe dysfunc-tion 67moderate 7mild-moderate 3mild dysfunctionand 0 no dysfunction

Evidence-Based Complementary and Alternative Medicine 5

0 5 10 15 200

20

40

60

IPSS after

TPSA

after

Figure 5 A correlation between tPSA and IPSS after treatment 119903 =minus221 119875 value = 0239

With the patientrsquos assessment on overall sexual satis-faction 27 had a severe dysfunction whilst 17 1723 and 16 of the rest of the patients had moderatemild-moderate mild and no dysfunction after treatmentSevere ED decreased with an increase in moderate symp-toms (Figure 6) Furthermore severe orgasmic dysfunctiondecreased after treatment with an increase in moderatedysfunction With regard to sexual desire mild to moder-ate dysfunction increased after treatment Severe and mildto moderate intercourse satisfaction dysfunction decreasedwhile moderate dysfunction increased Severe dysfunctionof overall satisfaction decreased with an increase in mildand no dysfunction (Figure 6) Furthermore there was asignificant positive association between the QoL and IPSSbefore treatment (119875 = 0002) (Figure 7) IPSS decreased aftertreatment with stable QoL (Figure 8)

In terms of age as age increased overall satisfactionwith ldquoprostate healthrdquo decreased This correlation howeverno longer existed after treatment (Figure 8) Correlationbetween ED and age indicated that ED was no longer age-dependent after treatment and had improved (Figure 9)Other insignificant associations with age occurred for sexualdesire intercourse satisfaction However overall satisfactionwhich was significantly age-dependent before treatment wasno longer a factor after treatment (Figure 10)

34 Biochemical Results

341 Routine Examinations From Table 2 RFT remainedrelatively unchanged after the 3-month study All LFTparameters increased slightly except for ALP that decreasedslightly but insignificantly However significant increaseswere observed in TBIL and IND BIL (119875 = 0001 119875 =0001 resp) (Table 3) The lipid profile remained virtuallyunchanged except forAPOA that increased significantly (119875 =0025) (Table 4)

342 Special Examinations From Table 5 total PSA (tPSA)reduced significantly from 279 plusmn 190 to 162 plusmn 118 ngmL

Table 2 A table showing renal function test (RFT) before and three(3) months after administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Sodium (mmolL) 1428 plusmn 66 1422 plusmn 66 0672Potassium (mmolL) 43 plusmn 06 43 plusmn 06 0609Urea (mmolL) 43 plusmn 14 44 plusmn 13 0664Creatinine (120583molL) 1059 plusmn 265 1060 plusmn 262 0981

Table 3 A table showing liver function test (LFT) before andthree (3) months after C membranaceus ethanolic root extractadministration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

AST (UL) 178 plusmn 44 186 plusmn 51 0391ALT (UL) 169 plusmn 65 179 plusmn 57 0465GGT (UL) 349 plusmn 153 358 plusmn 192 0729ALP (UL) 766 plusmn 523 688 plusmn 206 0441TP (gL) 744 plusmn 69 753 plusmn 90 0495ALB (gL) 442 plusmn 48 460 plusmn 72 0092TBIL (120583molL) 49 plusmn 26 83 plusmn 47 0001lowast

DBIL (120583molL) 29 plusmn 22 34 plusmn 25 0347IND BIL (120583molL) 20 plusmn 18 48 plusmn 45 0001lowastlowastSignificance at 95 confidence interval

Table 4 A table showing serum lipid levels before and three (3)months after C membranaceus ethanolic root extract administra-tion at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

TC (mmolL) 503 plusmn 112 519 plusmn 115 0423TG (mmolL) 115 plusmn 043 122 plusmn 056 0518HDL (mmolL) 076 plusmn 033 088 plusmn 032 0063LDL (mmolL) 374 plusmn 103 375 plusmn 102 0959APO A (gL) 131 plusmn 045 151 plusmn 047 0025lowast

APO B (gL) 058 plusmn 037 049 plusmn 013 0222APO BA ratio 281 plusmn 147 324 plusmn 127 0067lowastSignificance at 95 confidence interval

(119875 = 0002) Furthermore free PSA (fPSA) reduced from61 plusmn 48 to 39 plusmn 29ngmL (119875 = 0045) However PSA ratiodid not significantly change

35 Abdominopelvic Scan Data from the abdominopelvicscan showed that mean prostate volume reduced from 1018plusmn413 to 545 plusmn 248 cm3 The change over the 3-month periodwas significant (119875 = 0023)

6 Evidence-Based Complementary and Alternative Medicine

Erectile function before

Erectile function after

Orgasmic function before

Orgasmic function after

Sexual desire before

Sexual desire after

Intercourse sat before

Intercourse sat after

Overall sat before

Overall sat after

0 5 10 15 20 25

IIEF

Number of patients

No dysfunctionMild dysfunction Mild to moderate

Moderate dysfunction

Severe dysfunction dysfunction

Figure 6 A diagram showing the general overview of patientrsquos condition before and after treatment using the IIEF questionnaire

IPSS before

QL

befo

re

0 10 20 300

2

4

6

8

Figure 7 A correlation between QoL and IPSS before treatmentQoL before treatment strongly depended on IPSS 119903 = 0634119875 value= 0002

Table 5 Table showing the different levels of total PSA (tPSA) freePSA (fPSA) PSA ratio and prostate volume before and after three(3) months of administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

Total PSA (ngmL) 274 plusmn 190 162 plusmn 118 0002lowast

Free PSA (ngmL) 61 plusmn 48 39 plusmn 29 0045lowast

PSA ratio () 239 plusmn 187 246 plusmn 164 0813Prostate volume (cm3) 1018 plusmn 413 545 plusmn 248 0023lowastlowastSignificance at 95 confidence interval

0 5 10 15 200

1

2

3

4

IPSS after

QL

after

Figure 8 A correlation betweenQoL and IPSS after treatment QoLappear to be stable and not dependent on IPSS 119903 = 0061 and 119875 =0747

4 Discussion

BPH continues to be a major problem worldwide Whilenew pharmaceutical drugs are being sought for a gradualbut substantive shift to nutraceuticals and medicinal plantsis occurring globally Medicinal plants are being used by80 of the worldrsquos population In emerging economies itis the first line of medical support Nonetheless in someadvanced economies like Germany and Austria 90 usephytotherapeutic agents [7] The drive towards the use ofphytotherapeutic agents is a decision based on safety and sideeffects Mostmedicinal plants have been used for ages and areconsidered safe with fewer side effects

Evidence-Based Complementary and Alternative Medicine 7

Age (yrs)0 20 40 60 80 100

0

5

10

15

Orgasmic fxn before

Org

asm

ic fu

nctio

n

Orgasmic fxn after

Figure 9 A relationship between age and orgasmic function before(b) and after (a) treatment Orgasmic function remained relativelyunchanged Before 119903 = minus0179 119875 = 0344 after 119903 = minus0303 119875 =0103

Age (yrs)0 20 40 60 80 100

0

5

10

15

Ove

rall

satis

fact

ion

Overall sat beforeOverall sat after

Figure 10 A relationship between age and the overall patientsatisfaction before (b) and after (a) treatment Overall satisfactionwas determined by age before treatmentThis no longer existed aftertreatment Overall satisfaction appears to have stabilized Before119903 = minus0364 119875 = 0048 and after 119903 = 0024 119875 = 0901

C membranaceus aqueous root extract has been used inGhana for decades for BPH treatment The last decade hashowever witnessed a surge in scientific data on the effect ofC membranaceus in vitro and in vivo (animal studies)

Animal studies using normal Sprague-Dawley (S-D) ratsdemonstrated shrinking of the prostate and reduction inepithelial cells upon C membranaceus administration [19]Further to this BPH models (S-D rats) also demonstratedprostate volume and prostatic index reduction in C mem-branaceus treated rats alongside a finasteride positive control[16 20] Having obtained positive results in the aforemen-tioned studies it was incumbent to further demonstrateevidence of effectiveness to back anecdotal claims

Improvement of urinary symptoms and QoL are impor-tant issues for decision making in the management of BPHClinical symptoms of BPH can be categorized into obstruc-tive or irritative symptoms The former is associated with thenarrowing of the prostatic urethra with subsequent difficultyin passing urine or weak or trickling stream of urine whilethe latter relates to sensation of incomplete bladder emptyingurgency nocturia and pollakiuria Both categories affect theQoL IPSS is a patientrsquos assessment index used to rank severityof symptoms and QoL [21]

The IPSS questionnaire has been used extensively inmany phytotherapeutic studies Some polyherbal productshave been documented to improve IPSS Chimaphila umbel-lata Populus tremula Pulsatilla pratensis Equisetum arvenseTriticumaestivum [22] andChimaphila umbellata (L) BartonPopulus tremula Pulsatilla pratensis (L) Mill Equisetumarvense L and Triticum aestivum L [23] are made up of5 polyherbal plants Others like Serenoa repens (Bartram)SmallUrtica dioica L are biherbal preparations [24 25]Both the polyherbal and biherbal preparations have beendocumented to reduced IPSS A few monoherbal plants havereduced IPSS These include Serenoa repens Bartram [34]Urtica dioica L [27] and Pteris multifida [28] In the presentstudy C membranaceus ethanolic root extract (a monoherbalpreparation) showed a significant reduction in total IPSS ofthe subjects at the end of the study period (119875 = 0001)Furthermore QoL improved significantly (119875 = 0001)Admittedly BPH symptoms impeach onQoL of subjectsThisimprovement was not age related (Figure 7) Additionallya significant change in QoL was noticed Although otherfactors in the IPSS questionnaire such as erectile functionsexual desire and overall satisfaction improved changeswerenot significant However overall satisfaction was significantlyhigher in younger men and age differences did not existafter treatment On the down side orgasmic function andoverall intercourse satisfaction were slightly worse (Table 1)Intercourse satisfaction is perhaps an age related perceptionas older men showed less satisfaction before treatment thanyounger men However some degree of improvement seenwas largely due to the reduction in severe dysfunction relatedto intercourse (Figure 9) It appears that C membranaceusprimarily targets only the prostate without adverse effectson sexual function This is of interest since 5-120572-reductaseinhibitors and 120572-1-adrenoceptor blockers affect erectile func-tion The improved QoL and IPSS may largely thereforebe related to relief of symptoms It is worthy to note thatsexual desire after treatment was almost significant Thiswill need further investigations to determine whether Cmembranaceus possess some aphrodisiac properties

Severe ED however dropped after treatment (Figure 6)Further support to this is the fact that severe lower urinarytract symptoms (LUTS) disappeared after 3 months with acorresponding increase in those with mild and moderatesymptoms (Figure 6) The improvement could be attributedto improved urination although such directly related param-eters were not measured Vacciniummacrocarpon Aiton is anexample of a monoherbal plant that demonstrated improvedLUTS after administration of its extract [29] Further evi-dence of improved IPSS is accompanied by reduced PSA

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

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Disease Markers

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Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 2: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

2 Evidence-Based Complementary and Alternative Medicine

plants appear to be increasing worldwide Furthermore mostmen are reluctant to opt for surgical interventions for fearof losing potency and the perception of other adverse sideeffects The use of 5120572-reductase inhibitors and 120572-1 blockersfor BPH management has side effects including erectiledysfunction (ED) [5 6] Against this background subjectssuffering from BPH appreciably resort to CAM with asmuch as 90 of men in Austria and Germany depending onphytotherapy [7]

The role of phytotherapy in the health care deliverysystem is increasing It is estimated that the global marketfor medicinal plants is worth over $250 billion [8] Althoughthe economic data does not exist in Ghana medicinal plantpervoyeurs as well as their clients have increased BPHpatients in Ghana resort to the use of medicinal plants or acombination of medicinal plants and radiotherapy [9]

Traditional pharmacologic therapies although widelyused must be assessed for a favorable risk-benefit ratio Onesuch plant that has been studied over three decades in Ghanais Croton membranaceus Mull Arg (Euphorbiaceae) Thisplant is mostly available in three west African countriesnamely Ghana Nigeria and Niger In Ghana the plant ismostly found in the Krobo-Gyakiti forest reserve area in theEastern Region The root preparation of this medicinal planthas been dispensed to BPH patients at the Center for PlantMedicine Research (aWHOCenter) for the past 30 years [10]

The root extract is said to contain an alkaloid a coumarinditerpenoids and phytosterols [11ndash14] Compounds isolatedfrom the root extract include julocrotine scopoletin DL-threitol crotomembranafuran gomojoside H larixol 120573-sito-sterol 120573-sitosterol-3-O-glucoside stigmasterol and campes-terol Furthermore N[N-(2-methylbutanoyl) glutaminoyl]-2-phenylethylamine has recently been isolated [15] Thecrude ethanol extract of C membranaceus and julocrotinepossess 5-120572-reductase inhibitory activity [11] 5-120572-reductaseinhibitory activity is the underpinning mechanism for theapplication of finasteride for the treatment of BPH BPHtreatment with the aqueous root extract alongside finas-teride demonstrating similar efficacy as finasteride has beenreported in an animal model of BPH [16] Furthermorethe antiproliferative activity of C membranaceus on BPH-1cells has been demonstrated [17] Additionally the cytotoxicactivity of the methanolic extract of C membranaceus rootshas been shown against DLD-1 and MCF-7 cells Finally theaqueous root extract of the plant is nontoxic [18] Howeverno published data exist on its effect on human BPH patientsThis study aimed at observing the socioscientific markers ofBPH patients opting for the use of the ethanolic extract of Cmembranaceus

2 Materials and Methods

21 Plant Extract C membranaceus roots were harvestedfrom the forest area of the Eastern Region of Ghana tominimize the presence of contaminating herbicides and pes-ticidesThe root product was carefully extracted with ethanolaccording to the protocol of Appiah [10] Possible variationof content from batch to batch was averted by bulk harvest

and fingerprinting The extract was carefully checked forputative active ingredients(s) using chemical and biologicalparameters Analyses for lack of contamination by pesticidesherbicides heavy metals microbes and toxins were carriedout as part of the quality control procedures The Centerfor Plant Medicine Research (Mampong-Akuapem) furtherprocessed the freeze-dried extract into capsules (10mg percapsule) under strict quality control procedures with arecommended dose of 2 capsules tid The product has beenregistered with the Food and Drug Authority (FDA) Ghanaas URO 500 after satisfying the FDArsquos requirement

22 Experimental Site Eleven (11) centers nationwide havebeen allowed by the Ministry of Health Ghana to serve well-tested and prepared medicinal plants products alongsideorthodox drugs The Ghana Police Hospital Accra whichwas established in 1970 is a medium-size hospital with 100beds The hospital is currently undergoing expansion into anultramodern 400-bed facility It serves as one of the centerscurrently approved by the Ministry of Health to administermedicinal plant products alongside orthodox medicine Thecenter was therefore selected for this study

23 Patients The study obtained ethical clearance fromthe University of Ghana School of Biomedical and AlliedHealth Sciences with ethics clearance number SAHS-ETSAHSPSMML09AA26A2012-2013 for an observa-tional study to be conducted The study complied with theHelsinki Declaration of 1964 with revision in October 2008Patients opting for the use of the herbal remedy and whowere willing to be part of the study were given informedconsent forms Forms were duly filled and the group formedthe cohort Patients were between the ages of 50 and 72 yearsFurthermore patients came from all walks of life howevermost of them were from the capital city of Ghana Accra withfew from Togo and Nigeria The cohort of 33 patients whoopted for phytomedicine was not on any other medicationfor BPH management Furthermore these patients wereunder medical supervision of the urologist on the protocoldevelopment team Patientswere advised to carefully note anyadverse effects and immediately report such using the hotlineprovided

24 Research Instruments Four main research instrumentswere employed The first was the International ProstateSymptom Score (IPSS) questionnaire followed by the sec-ond the International Index of Erectile Function (IIEF)questionnaire The third research instrument was bloodsampling for routine and special biochemical tests and thelast abdominopelvic ultrasonography Research instrumentswere employed before and after 3 months of treatment

241 IPSSQuestionnaire TheIPSS is constructed on answersto seven questions concerning urinary symptoms and onequestion concerning QoL Each question concerning symp-toms in passing urine allowed the patient to choose 1 outof 6 answers representing increasing severity of a particularsymptomThe answers were assigned points from 0 to 5 with

Evidence-Based Complementary and Alternative Medicine 3

5 signifying worsening symptoms The total score thereforeranged from 0 to 35 (asymptomatic to very symptomatic)Symptoms were graded alongside the following incompleteemptying frequency intermittency urgency weak streamstraining and nocturia These first 7 questions of the IPSSwere identical to the questions appearing on the AmericanUrological Association (AUA) Symptom Index The eighthquestion dealt with the patientrsquos perceived QoL and wasscored 0ndash6 with 6 representing a terrible quality of life Com-puted results were categorized as follows mild (symptomscore less than or equal to 7)moderate (symptom score range8ndash19) and severe (symptom score range 20ndash35)

242 IIEF Questionnaire IIEF was based on the effects oferectile problems on onersquos reproductive health life over thepast 4 weeks The 15-point questionnaire finally categorizedanswers into broad areas of erectile function orgasmicfunction sexual desire intercourse satisfaction and overallsatisfaction Clinical interpretation ranged from the lowestscore (no dysfunction) to the highest (severe dysfunction)

243 Biochemical Assays Five milliliters (5mL) of bloodsamples was obtained from the patients before and aftertreatment for various blood tests as part of the urologistrsquosrequest Blood examinations were of two categories routineexaminations and special examinations

(1) Routine Examinations Renal function test (RFT) liverfunction test (LFT) and the lipid profile were performedRFT was made up of urea creatinine Na+ and K+ LFTcomprised total-direct and indirect bilirubin (TBIL DBILand IND BIL resp) aspartate transaminase (AST) alaninetransaminase (ALT) gamma-glutamyl transferase (GGT)alkaline phosphatase (ALP) total protein (TP) and albumin(ALB) Total cholesterol (TC) triglyceride (TG) high den-sity lipoprotein cholesterol (HDL) low density lipoproteincholesterol (LDL) and apolipoproteins A and B made up thelipid profile LDLwas calculated using Friedewealdrsquos equation([LDL-chol] = [Total chol] minus [HDL-chol] minus ([TG]22)) Allroutine examinations were performed using the Vitros 5 IFSChemistry analyzer (New York USA)

(2) Special Examinations Free and total PSA (fPSA andtPSA resp) were performed using Accu-Bind free andtotal PSA ELISA kits were purchased from Monobind Inc(California USA) The tests were performed according tothe manufacturerrsquos instructions In brief serum samples wereadded alongside standards to a highly specific monoclonalanti-PSA antibody coated onto the surface of wells Afterthe first wash an antibody-HRP enzyme conjugate wasapplied to form a sandwich complex on the well surfaceExcess reagents were washed off followed by the additionof 331015840551015840-tetramethylbenzidine (TMB)hydrogen peroxide(substrate) to react with the HRP After stopping the reactionwith sulfuric acid the final chromogen was then read at450 nm using a microplate reader PSA ratio was calculatedas fPSATPSA in

244 Abdominopelvic Scan The SonoScape Digital ColourDoppler Ultrasound System 551ndash6000 (Shenzhen China)was used Patients were asked to drink approximately 15 Lof water and allowed to wait for 1-2 hours before the scanwas performed The purpose of this preparation was to getthe urinary bladder filled with urine so as to act as anacoustic window through which the prostate could better bevisualized Patients were then positioned on the ultrasoundcouch With the pelvic area exposed a liquid gel was appliedon the probe surface to improve the contact between thepatientrsquos skin and the probe surface The prostate volumeand bladder volume at full capacity were obtained After thescanning procedure patients were then asked to void urineafter which a second scan to determine the postvoid residualvolume of the urinary bladder was performed

25 Statistical Analysis Data for the studywas analyzed usingGraphpad Prisms 601 Studentrsquos t-test for paired data wasperformedDescriptive statisticswas presented asmeanplusmn SDPearsonrsquos correlation analysis was performed to determineassociations

3 Results

31 Demographic Data In all 30 clinically diagnosed BPHpatients attending the urology and phytomedicine clinicswith an average age of 66 plusmn 11 years completed the 3-monthobservational study 3 others were excluded for noncompli-ance No report of adverse effects was registered by any ofthe patients during the study However one diabetic patientreported improved glycemic index which further supportsour unpublished data of possible hypoglycemic effect of Cmembranaceus

32 IPSS IPSS relates to the degree of BPH or prostate cancersymptoms experienced Only BPH patients were used forthe study Thirty-seven percent (37) of the patients hadsevere prostate symptoms 40 moderate symptoms and23mild symptoms before treatment with C membranaceusroot extract Fifty-seven (57) and 43 of the patients hadmoderate and mild symptoms respectively after treatmentHowever there was no patient with severe prostate symptomafter treatment

IPSS improved significantly from 151plusmn87units to 103plusmn47 units signifying improved symptoms The decrease wassignificant (119875 = 0005) Additionally QoL improved andthis was highly significant (119875 = 0001) (Table 1) Overallprostate symptom score indicated that severe symptomsdisappeared after treatment while mild and moderate symp-toms increased (Figure 1) In general 33 of the patientsrecruited for this study were happy about their state of healthbefore treatment while 67 of them were unhappy Aftertreatment 83 were happy about their present state of healthwhile 17 remained unhappy A negative correlation betweenQoL and age was observed after treatment although this wasnot significant (Figure 2) Furthermore total IPSS did notsignificantly depend on age (Figure 3) or tPSA levels (Figures4 and 5)

4 Evidence-Based Complementary and Alternative Medicine

7

12

11

13

17

0

0 2 4 6 8 10 12 14 16 18

TIPSS 2TIPSS 1

Severelysymptomatic

Moderatelysymptomatic

Mildlysymptomatic

Figure 1 A diagram showing the prostate symptom score (IPSS)before and after 3 months of plant extract administration

Age (yrs)0 20 40 60 80 100

0

2

4

6

8

QL before

Qua

lity

of li

fe

QL after

Figure 2 A relationship between age and QoL before (b) and after(a) treatment 119903 (b) = minus0010 119903 (a) = minus0330 and 119875 value (b) = 0956119875 value (a) = 0075

Table 1 Table showing prostate symptom score sexual functionand quality of life in BPH patients after three (3) months of Cmembranaceus ethanolic root extract administration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Age (yrs) 660 plusmn 110Total IPSS 151 plusmn 87 103 plusmn 47 0001lowast

Erectile function 100 plusmn 60 97 plusmn 41 0751Orgasmic function 26 plusmn 25 29 plusmn 24 0620Sexual desire 59 plusmn 25 50 plusmn 21 0053Intercourse satisfaction 38 plusmn 32 46 plusmn 25 0154Overall satisfaction 52 plusmn 36 48 plusmn 29 0598Quality of life 33 plusmn 16 17 plusmn 09 0001lowastlowastSignificance at 95 confidence interval

33 IIED Thirty percent (30) of the patients had severeerectile dysfunction 40 moderate dysfunction 24 mild-moderate dysfunction 3 mild dysfunction and 3 nodysfunction before treatment After treatment 20 of the

Age (yrs)0 20 40 60 80 100

0

10

20

30

Total IPSS before

Tota

l IPS

S

Total IPSS after

Figure 3 A relationship between age and IPSS before (b) and after(a) treatment 119903 (b) = 0005 119903 (a) = 0247 and 119875 value (b) = 0981 119875value (a) = 0189

IPSS before

TPSA

bef

ore

0 10 20 300

50

100

150

Figure 4 A correlation between tPSA and IPSS before treatment119903 = minus0089 119875 value = 0640

patients had severe erectile dysfunction 43 moderateand 37 mild-moderate dysfunction No patient had milddysfunction or no dysfunction after treatment

With regard to orgasmic dysfunction 53 had severeorgasmic dysfunction 27moderate 13mild-moderate 4mild and 3 no dysfunction before treatment After treat-ment 37 had severe orgasmic dysfunction 57 moderate3 mild-moderate 0 mild and 3 no dysfunction

Patients with severe dysfunction in sexual desire formed6 Twenty percent (20) 37 27 and 10 hadmoderatemild-moderate mild and no dysfunction in sexual desirerespectively before treatment compared to 10 severe 27moderate 50 mild-moderate 6 mild and 7 no dys-function after treatment Additionally 40 of the patientshad severe dysfunction 33 moderate 24 mild-moderate3 mild and 0 no dysfunction in intercourse satisfactionbefore treatment After treatment 23 had severe dysfunc-tion 67moderate 7mild-moderate 3mild dysfunctionand 0 no dysfunction

Evidence-Based Complementary and Alternative Medicine 5

0 5 10 15 200

20

40

60

IPSS after

TPSA

after

Figure 5 A correlation between tPSA and IPSS after treatment 119903 =minus221 119875 value = 0239

With the patientrsquos assessment on overall sexual satis-faction 27 had a severe dysfunction whilst 17 1723 and 16 of the rest of the patients had moderatemild-moderate mild and no dysfunction after treatmentSevere ED decreased with an increase in moderate symp-toms (Figure 6) Furthermore severe orgasmic dysfunctiondecreased after treatment with an increase in moderatedysfunction With regard to sexual desire mild to moder-ate dysfunction increased after treatment Severe and mildto moderate intercourse satisfaction dysfunction decreasedwhile moderate dysfunction increased Severe dysfunctionof overall satisfaction decreased with an increase in mildand no dysfunction (Figure 6) Furthermore there was asignificant positive association between the QoL and IPSSbefore treatment (119875 = 0002) (Figure 7) IPSS decreased aftertreatment with stable QoL (Figure 8)

In terms of age as age increased overall satisfactionwith ldquoprostate healthrdquo decreased This correlation howeverno longer existed after treatment (Figure 8) Correlationbetween ED and age indicated that ED was no longer age-dependent after treatment and had improved (Figure 9)Other insignificant associations with age occurred for sexualdesire intercourse satisfaction However overall satisfactionwhich was significantly age-dependent before treatment wasno longer a factor after treatment (Figure 10)

34 Biochemical Results

341 Routine Examinations From Table 2 RFT remainedrelatively unchanged after the 3-month study All LFTparameters increased slightly except for ALP that decreasedslightly but insignificantly However significant increaseswere observed in TBIL and IND BIL (119875 = 0001 119875 =0001 resp) (Table 3) The lipid profile remained virtuallyunchanged except forAPOA that increased significantly (119875 =0025) (Table 4)

342 Special Examinations From Table 5 total PSA (tPSA)reduced significantly from 279 plusmn 190 to 162 plusmn 118 ngmL

Table 2 A table showing renal function test (RFT) before and three(3) months after administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Sodium (mmolL) 1428 plusmn 66 1422 plusmn 66 0672Potassium (mmolL) 43 plusmn 06 43 plusmn 06 0609Urea (mmolL) 43 plusmn 14 44 plusmn 13 0664Creatinine (120583molL) 1059 plusmn 265 1060 plusmn 262 0981

Table 3 A table showing liver function test (LFT) before andthree (3) months after C membranaceus ethanolic root extractadministration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

AST (UL) 178 plusmn 44 186 plusmn 51 0391ALT (UL) 169 plusmn 65 179 plusmn 57 0465GGT (UL) 349 plusmn 153 358 plusmn 192 0729ALP (UL) 766 plusmn 523 688 plusmn 206 0441TP (gL) 744 plusmn 69 753 plusmn 90 0495ALB (gL) 442 plusmn 48 460 plusmn 72 0092TBIL (120583molL) 49 plusmn 26 83 plusmn 47 0001lowast

DBIL (120583molL) 29 plusmn 22 34 plusmn 25 0347IND BIL (120583molL) 20 plusmn 18 48 plusmn 45 0001lowastlowastSignificance at 95 confidence interval

Table 4 A table showing serum lipid levels before and three (3)months after C membranaceus ethanolic root extract administra-tion at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

TC (mmolL) 503 plusmn 112 519 plusmn 115 0423TG (mmolL) 115 plusmn 043 122 plusmn 056 0518HDL (mmolL) 076 plusmn 033 088 plusmn 032 0063LDL (mmolL) 374 plusmn 103 375 plusmn 102 0959APO A (gL) 131 plusmn 045 151 plusmn 047 0025lowast

APO B (gL) 058 plusmn 037 049 plusmn 013 0222APO BA ratio 281 plusmn 147 324 plusmn 127 0067lowastSignificance at 95 confidence interval

(119875 = 0002) Furthermore free PSA (fPSA) reduced from61 plusmn 48 to 39 plusmn 29ngmL (119875 = 0045) However PSA ratiodid not significantly change

35 Abdominopelvic Scan Data from the abdominopelvicscan showed that mean prostate volume reduced from 1018plusmn413 to 545 plusmn 248 cm3 The change over the 3-month periodwas significant (119875 = 0023)

6 Evidence-Based Complementary and Alternative Medicine

Erectile function before

Erectile function after

Orgasmic function before

Orgasmic function after

Sexual desire before

Sexual desire after

Intercourse sat before

Intercourse sat after

Overall sat before

Overall sat after

0 5 10 15 20 25

IIEF

Number of patients

No dysfunctionMild dysfunction Mild to moderate

Moderate dysfunction

Severe dysfunction dysfunction

Figure 6 A diagram showing the general overview of patientrsquos condition before and after treatment using the IIEF questionnaire

IPSS before

QL

befo

re

0 10 20 300

2

4

6

8

Figure 7 A correlation between QoL and IPSS before treatmentQoL before treatment strongly depended on IPSS 119903 = 0634119875 value= 0002

Table 5 Table showing the different levels of total PSA (tPSA) freePSA (fPSA) PSA ratio and prostate volume before and after three(3) months of administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

Total PSA (ngmL) 274 plusmn 190 162 plusmn 118 0002lowast

Free PSA (ngmL) 61 plusmn 48 39 plusmn 29 0045lowast

PSA ratio () 239 plusmn 187 246 plusmn 164 0813Prostate volume (cm3) 1018 plusmn 413 545 plusmn 248 0023lowastlowastSignificance at 95 confidence interval

0 5 10 15 200

1

2

3

4

IPSS after

QL

after

Figure 8 A correlation betweenQoL and IPSS after treatment QoLappear to be stable and not dependent on IPSS 119903 = 0061 and 119875 =0747

4 Discussion

BPH continues to be a major problem worldwide Whilenew pharmaceutical drugs are being sought for a gradualbut substantive shift to nutraceuticals and medicinal plantsis occurring globally Medicinal plants are being used by80 of the worldrsquos population In emerging economies itis the first line of medical support Nonetheless in someadvanced economies like Germany and Austria 90 usephytotherapeutic agents [7] The drive towards the use ofphytotherapeutic agents is a decision based on safety and sideeffects Mostmedicinal plants have been used for ages and areconsidered safe with fewer side effects

Evidence-Based Complementary and Alternative Medicine 7

Age (yrs)0 20 40 60 80 100

0

5

10

15

Orgasmic fxn before

Org

asm

ic fu

nctio

n

Orgasmic fxn after

Figure 9 A relationship between age and orgasmic function before(b) and after (a) treatment Orgasmic function remained relativelyunchanged Before 119903 = minus0179 119875 = 0344 after 119903 = minus0303 119875 =0103

Age (yrs)0 20 40 60 80 100

0

5

10

15

Ove

rall

satis

fact

ion

Overall sat beforeOverall sat after

Figure 10 A relationship between age and the overall patientsatisfaction before (b) and after (a) treatment Overall satisfactionwas determined by age before treatmentThis no longer existed aftertreatment Overall satisfaction appears to have stabilized Before119903 = minus0364 119875 = 0048 and after 119903 = 0024 119875 = 0901

C membranaceus aqueous root extract has been used inGhana for decades for BPH treatment The last decade hashowever witnessed a surge in scientific data on the effect ofC membranaceus in vitro and in vivo (animal studies)

Animal studies using normal Sprague-Dawley (S-D) ratsdemonstrated shrinking of the prostate and reduction inepithelial cells upon C membranaceus administration [19]Further to this BPH models (S-D rats) also demonstratedprostate volume and prostatic index reduction in C mem-branaceus treated rats alongside a finasteride positive control[16 20] Having obtained positive results in the aforemen-tioned studies it was incumbent to further demonstrateevidence of effectiveness to back anecdotal claims

Improvement of urinary symptoms and QoL are impor-tant issues for decision making in the management of BPHClinical symptoms of BPH can be categorized into obstruc-tive or irritative symptoms The former is associated with thenarrowing of the prostatic urethra with subsequent difficultyin passing urine or weak or trickling stream of urine whilethe latter relates to sensation of incomplete bladder emptyingurgency nocturia and pollakiuria Both categories affect theQoL IPSS is a patientrsquos assessment index used to rank severityof symptoms and QoL [21]

The IPSS questionnaire has been used extensively inmany phytotherapeutic studies Some polyherbal productshave been documented to improve IPSS Chimaphila umbel-lata Populus tremula Pulsatilla pratensis Equisetum arvenseTriticumaestivum [22] andChimaphila umbellata (L) BartonPopulus tremula Pulsatilla pratensis (L) Mill Equisetumarvense L and Triticum aestivum L [23] are made up of5 polyherbal plants Others like Serenoa repens (Bartram)SmallUrtica dioica L are biherbal preparations [24 25]Both the polyherbal and biherbal preparations have beendocumented to reduced IPSS A few monoherbal plants havereduced IPSS These include Serenoa repens Bartram [34]Urtica dioica L [27] and Pteris multifida [28] In the presentstudy C membranaceus ethanolic root extract (a monoherbalpreparation) showed a significant reduction in total IPSS ofthe subjects at the end of the study period (119875 = 0001)Furthermore QoL improved significantly (119875 = 0001)Admittedly BPH symptoms impeach onQoL of subjectsThisimprovement was not age related (Figure 7) Additionallya significant change in QoL was noticed Although otherfactors in the IPSS questionnaire such as erectile functionsexual desire and overall satisfaction improved changeswerenot significant However overall satisfaction was significantlyhigher in younger men and age differences did not existafter treatment On the down side orgasmic function andoverall intercourse satisfaction were slightly worse (Table 1)Intercourse satisfaction is perhaps an age related perceptionas older men showed less satisfaction before treatment thanyounger men However some degree of improvement seenwas largely due to the reduction in severe dysfunction relatedto intercourse (Figure 9) It appears that C membranaceusprimarily targets only the prostate without adverse effectson sexual function This is of interest since 5-120572-reductaseinhibitors and 120572-1-adrenoceptor blockers affect erectile func-tion The improved QoL and IPSS may largely thereforebe related to relief of symptoms It is worthy to note thatsexual desire after treatment was almost significant Thiswill need further investigations to determine whether Cmembranaceus possess some aphrodisiac properties

Severe ED however dropped after treatment (Figure 6)Further support to this is the fact that severe lower urinarytract symptoms (LUTS) disappeared after 3 months with acorresponding increase in those with mild and moderatesymptoms (Figure 6) The improvement could be attributedto improved urination although such directly related param-eters were not measured Vacciniummacrocarpon Aiton is anexample of a monoherbal plant that demonstrated improvedLUTS after administration of its extract [29] Further evi-dence of improved IPSS is accompanied by reduced PSA

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

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Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 3: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

Evidence-Based Complementary and Alternative Medicine 3

5 signifying worsening symptoms The total score thereforeranged from 0 to 35 (asymptomatic to very symptomatic)Symptoms were graded alongside the following incompleteemptying frequency intermittency urgency weak streamstraining and nocturia These first 7 questions of the IPSSwere identical to the questions appearing on the AmericanUrological Association (AUA) Symptom Index The eighthquestion dealt with the patientrsquos perceived QoL and wasscored 0ndash6 with 6 representing a terrible quality of life Com-puted results were categorized as follows mild (symptomscore less than or equal to 7)moderate (symptom score range8ndash19) and severe (symptom score range 20ndash35)

242 IIEF Questionnaire IIEF was based on the effects oferectile problems on onersquos reproductive health life over thepast 4 weeks The 15-point questionnaire finally categorizedanswers into broad areas of erectile function orgasmicfunction sexual desire intercourse satisfaction and overallsatisfaction Clinical interpretation ranged from the lowestscore (no dysfunction) to the highest (severe dysfunction)

243 Biochemical Assays Five milliliters (5mL) of bloodsamples was obtained from the patients before and aftertreatment for various blood tests as part of the urologistrsquosrequest Blood examinations were of two categories routineexaminations and special examinations

(1) Routine Examinations Renal function test (RFT) liverfunction test (LFT) and the lipid profile were performedRFT was made up of urea creatinine Na+ and K+ LFTcomprised total-direct and indirect bilirubin (TBIL DBILand IND BIL resp) aspartate transaminase (AST) alaninetransaminase (ALT) gamma-glutamyl transferase (GGT)alkaline phosphatase (ALP) total protein (TP) and albumin(ALB) Total cholesterol (TC) triglyceride (TG) high den-sity lipoprotein cholesterol (HDL) low density lipoproteincholesterol (LDL) and apolipoproteins A and B made up thelipid profile LDLwas calculated using Friedewealdrsquos equation([LDL-chol] = [Total chol] minus [HDL-chol] minus ([TG]22)) Allroutine examinations were performed using the Vitros 5 IFSChemistry analyzer (New York USA)

(2) Special Examinations Free and total PSA (fPSA andtPSA resp) were performed using Accu-Bind free andtotal PSA ELISA kits were purchased from Monobind Inc(California USA) The tests were performed according tothe manufacturerrsquos instructions In brief serum samples wereadded alongside standards to a highly specific monoclonalanti-PSA antibody coated onto the surface of wells Afterthe first wash an antibody-HRP enzyme conjugate wasapplied to form a sandwich complex on the well surfaceExcess reagents were washed off followed by the additionof 331015840551015840-tetramethylbenzidine (TMB)hydrogen peroxide(substrate) to react with the HRP After stopping the reactionwith sulfuric acid the final chromogen was then read at450 nm using a microplate reader PSA ratio was calculatedas fPSATPSA in

244 Abdominopelvic Scan The SonoScape Digital ColourDoppler Ultrasound System 551ndash6000 (Shenzhen China)was used Patients were asked to drink approximately 15 Lof water and allowed to wait for 1-2 hours before the scanwas performed The purpose of this preparation was to getthe urinary bladder filled with urine so as to act as anacoustic window through which the prostate could better bevisualized Patients were then positioned on the ultrasoundcouch With the pelvic area exposed a liquid gel was appliedon the probe surface to improve the contact between thepatientrsquos skin and the probe surface The prostate volumeand bladder volume at full capacity were obtained After thescanning procedure patients were then asked to void urineafter which a second scan to determine the postvoid residualvolume of the urinary bladder was performed

25 Statistical Analysis Data for the studywas analyzed usingGraphpad Prisms 601 Studentrsquos t-test for paired data wasperformedDescriptive statisticswas presented asmeanplusmn SDPearsonrsquos correlation analysis was performed to determineassociations

3 Results

31 Demographic Data In all 30 clinically diagnosed BPHpatients attending the urology and phytomedicine clinicswith an average age of 66 plusmn 11 years completed the 3-monthobservational study 3 others were excluded for noncompli-ance No report of adverse effects was registered by any ofthe patients during the study However one diabetic patientreported improved glycemic index which further supportsour unpublished data of possible hypoglycemic effect of Cmembranaceus

32 IPSS IPSS relates to the degree of BPH or prostate cancersymptoms experienced Only BPH patients were used forthe study Thirty-seven percent (37) of the patients hadsevere prostate symptoms 40 moderate symptoms and23mild symptoms before treatment with C membranaceusroot extract Fifty-seven (57) and 43 of the patients hadmoderate and mild symptoms respectively after treatmentHowever there was no patient with severe prostate symptomafter treatment

IPSS improved significantly from 151plusmn87units to 103plusmn47 units signifying improved symptoms The decrease wassignificant (119875 = 0005) Additionally QoL improved andthis was highly significant (119875 = 0001) (Table 1) Overallprostate symptom score indicated that severe symptomsdisappeared after treatment while mild and moderate symp-toms increased (Figure 1) In general 33 of the patientsrecruited for this study were happy about their state of healthbefore treatment while 67 of them were unhappy Aftertreatment 83 were happy about their present state of healthwhile 17 remained unhappy A negative correlation betweenQoL and age was observed after treatment although this wasnot significant (Figure 2) Furthermore total IPSS did notsignificantly depend on age (Figure 3) or tPSA levels (Figures4 and 5)

4 Evidence-Based Complementary and Alternative Medicine

7

12

11

13

17

0

0 2 4 6 8 10 12 14 16 18

TIPSS 2TIPSS 1

Severelysymptomatic

Moderatelysymptomatic

Mildlysymptomatic

Figure 1 A diagram showing the prostate symptom score (IPSS)before and after 3 months of plant extract administration

Age (yrs)0 20 40 60 80 100

0

2

4

6

8

QL before

Qua

lity

of li

fe

QL after

Figure 2 A relationship between age and QoL before (b) and after(a) treatment 119903 (b) = minus0010 119903 (a) = minus0330 and 119875 value (b) = 0956119875 value (a) = 0075

Table 1 Table showing prostate symptom score sexual functionand quality of life in BPH patients after three (3) months of Cmembranaceus ethanolic root extract administration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Age (yrs) 660 plusmn 110Total IPSS 151 plusmn 87 103 plusmn 47 0001lowast

Erectile function 100 plusmn 60 97 plusmn 41 0751Orgasmic function 26 plusmn 25 29 plusmn 24 0620Sexual desire 59 plusmn 25 50 plusmn 21 0053Intercourse satisfaction 38 plusmn 32 46 plusmn 25 0154Overall satisfaction 52 plusmn 36 48 plusmn 29 0598Quality of life 33 plusmn 16 17 plusmn 09 0001lowastlowastSignificance at 95 confidence interval

33 IIED Thirty percent (30) of the patients had severeerectile dysfunction 40 moderate dysfunction 24 mild-moderate dysfunction 3 mild dysfunction and 3 nodysfunction before treatment After treatment 20 of the

Age (yrs)0 20 40 60 80 100

0

10

20

30

Total IPSS before

Tota

l IPS

S

Total IPSS after

Figure 3 A relationship between age and IPSS before (b) and after(a) treatment 119903 (b) = 0005 119903 (a) = 0247 and 119875 value (b) = 0981 119875value (a) = 0189

IPSS before

TPSA

bef

ore

0 10 20 300

50

100

150

Figure 4 A correlation between tPSA and IPSS before treatment119903 = minus0089 119875 value = 0640

patients had severe erectile dysfunction 43 moderateand 37 mild-moderate dysfunction No patient had milddysfunction or no dysfunction after treatment

With regard to orgasmic dysfunction 53 had severeorgasmic dysfunction 27moderate 13mild-moderate 4mild and 3 no dysfunction before treatment After treat-ment 37 had severe orgasmic dysfunction 57 moderate3 mild-moderate 0 mild and 3 no dysfunction

Patients with severe dysfunction in sexual desire formed6 Twenty percent (20) 37 27 and 10 hadmoderatemild-moderate mild and no dysfunction in sexual desirerespectively before treatment compared to 10 severe 27moderate 50 mild-moderate 6 mild and 7 no dys-function after treatment Additionally 40 of the patientshad severe dysfunction 33 moderate 24 mild-moderate3 mild and 0 no dysfunction in intercourse satisfactionbefore treatment After treatment 23 had severe dysfunc-tion 67moderate 7mild-moderate 3mild dysfunctionand 0 no dysfunction

Evidence-Based Complementary and Alternative Medicine 5

0 5 10 15 200

20

40

60

IPSS after

TPSA

after

Figure 5 A correlation between tPSA and IPSS after treatment 119903 =minus221 119875 value = 0239

With the patientrsquos assessment on overall sexual satis-faction 27 had a severe dysfunction whilst 17 1723 and 16 of the rest of the patients had moderatemild-moderate mild and no dysfunction after treatmentSevere ED decreased with an increase in moderate symp-toms (Figure 6) Furthermore severe orgasmic dysfunctiondecreased after treatment with an increase in moderatedysfunction With regard to sexual desire mild to moder-ate dysfunction increased after treatment Severe and mildto moderate intercourse satisfaction dysfunction decreasedwhile moderate dysfunction increased Severe dysfunctionof overall satisfaction decreased with an increase in mildand no dysfunction (Figure 6) Furthermore there was asignificant positive association between the QoL and IPSSbefore treatment (119875 = 0002) (Figure 7) IPSS decreased aftertreatment with stable QoL (Figure 8)

In terms of age as age increased overall satisfactionwith ldquoprostate healthrdquo decreased This correlation howeverno longer existed after treatment (Figure 8) Correlationbetween ED and age indicated that ED was no longer age-dependent after treatment and had improved (Figure 9)Other insignificant associations with age occurred for sexualdesire intercourse satisfaction However overall satisfactionwhich was significantly age-dependent before treatment wasno longer a factor after treatment (Figure 10)

34 Biochemical Results

341 Routine Examinations From Table 2 RFT remainedrelatively unchanged after the 3-month study All LFTparameters increased slightly except for ALP that decreasedslightly but insignificantly However significant increaseswere observed in TBIL and IND BIL (119875 = 0001 119875 =0001 resp) (Table 3) The lipid profile remained virtuallyunchanged except forAPOA that increased significantly (119875 =0025) (Table 4)

342 Special Examinations From Table 5 total PSA (tPSA)reduced significantly from 279 plusmn 190 to 162 plusmn 118 ngmL

Table 2 A table showing renal function test (RFT) before and three(3) months after administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Sodium (mmolL) 1428 plusmn 66 1422 plusmn 66 0672Potassium (mmolL) 43 plusmn 06 43 plusmn 06 0609Urea (mmolL) 43 plusmn 14 44 plusmn 13 0664Creatinine (120583molL) 1059 plusmn 265 1060 plusmn 262 0981

Table 3 A table showing liver function test (LFT) before andthree (3) months after C membranaceus ethanolic root extractadministration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

AST (UL) 178 plusmn 44 186 plusmn 51 0391ALT (UL) 169 plusmn 65 179 plusmn 57 0465GGT (UL) 349 plusmn 153 358 plusmn 192 0729ALP (UL) 766 plusmn 523 688 plusmn 206 0441TP (gL) 744 plusmn 69 753 plusmn 90 0495ALB (gL) 442 plusmn 48 460 plusmn 72 0092TBIL (120583molL) 49 plusmn 26 83 plusmn 47 0001lowast

DBIL (120583molL) 29 plusmn 22 34 plusmn 25 0347IND BIL (120583molL) 20 plusmn 18 48 plusmn 45 0001lowastlowastSignificance at 95 confidence interval

Table 4 A table showing serum lipid levels before and three (3)months after C membranaceus ethanolic root extract administra-tion at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

TC (mmolL) 503 plusmn 112 519 plusmn 115 0423TG (mmolL) 115 plusmn 043 122 plusmn 056 0518HDL (mmolL) 076 plusmn 033 088 plusmn 032 0063LDL (mmolL) 374 plusmn 103 375 plusmn 102 0959APO A (gL) 131 plusmn 045 151 plusmn 047 0025lowast

APO B (gL) 058 plusmn 037 049 plusmn 013 0222APO BA ratio 281 plusmn 147 324 plusmn 127 0067lowastSignificance at 95 confidence interval

(119875 = 0002) Furthermore free PSA (fPSA) reduced from61 plusmn 48 to 39 plusmn 29ngmL (119875 = 0045) However PSA ratiodid not significantly change

35 Abdominopelvic Scan Data from the abdominopelvicscan showed that mean prostate volume reduced from 1018plusmn413 to 545 plusmn 248 cm3 The change over the 3-month periodwas significant (119875 = 0023)

6 Evidence-Based Complementary and Alternative Medicine

Erectile function before

Erectile function after

Orgasmic function before

Orgasmic function after

Sexual desire before

Sexual desire after

Intercourse sat before

Intercourse sat after

Overall sat before

Overall sat after

0 5 10 15 20 25

IIEF

Number of patients

No dysfunctionMild dysfunction Mild to moderate

Moderate dysfunction

Severe dysfunction dysfunction

Figure 6 A diagram showing the general overview of patientrsquos condition before and after treatment using the IIEF questionnaire

IPSS before

QL

befo

re

0 10 20 300

2

4

6

8

Figure 7 A correlation between QoL and IPSS before treatmentQoL before treatment strongly depended on IPSS 119903 = 0634119875 value= 0002

Table 5 Table showing the different levels of total PSA (tPSA) freePSA (fPSA) PSA ratio and prostate volume before and after three(3) months of administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

Total PSA (ngmL) 274 plusmn 190 162 plusmn 118 0002lowast

Free PSA (ngmL) 61 plusmn 48 39 plusmn 29 0045lowast

PSA ratio () 239 plusmn 187 246 plusmn 164 0813Prostate volume (cm3) 1018 plusmn 413 545 plusmn 248 0023lowastlowastSignificance at 95 confidence interval

0 5 10 15 200

1

2

3

4

IPSS after

QL

after

Figure 8 A correlation betweenQoL and IPSS after treatment QoLappear to be stable and not dependent on IPSS 119903 = 0061 and 119875 =0747

4 Discussion

BPH continues to be a major problem worldwide Whilenew pharmaceutical drugs are being sought for a gradualbut substantive shift to nutraceuticals and medicinal plantsis occurring globally Medicinal plants are being used by80 of the worldrsquos population In emerging economies itis the first line of medical support Nonetheless in someadvanced economies like Germany and Austria 90 usephytotherapeutic agents [7] The drive towards the use ofphytotherapeutic agents is a decision based on safety and sideeffects Mostmedicinal plants have been used for ages and areconsidered safe with fewer side effects

Evidence-Based Complementary and Alternative Medicine 7

Age (yrs)0 20 40 60 80 100

0

5

10

15

Orgasmic fxn before

Org

asm

ic fu

nctio

n

Orgasmic fxn after

Figure 9 A relationship between age and orgasmic function before(b) and after (a) treatment Orgasmic function remained relativelyunchanged Before 119903 = minus0179 119875 = 0344 after 119903 = minus0303 119875 =0103

Age (yrs)0 20 40 60 80 100

0

5

10

15

Ove

rall

satis

fact

ion

Overall sat beforeOverall sat after

Figure 10 A relationship between age and the overall patientsatisfaction before (b) and after (a) treatment Overall satisfactionwas determined by age before treatmentThis no longer existed aftertreatment Overall satisfaction appears to have stabilized Before119903 = minus0364 119875 = 0048 and after 119903 = 0024 119875 = 0901

C membranaceus aqueous root extract has been used inGhana for decades for BPH treatment The last decade hashowever witnessed a surge in scientific data on the effect ofC membranaceus in vitro and in vivo (animal studies)

Animal studies using normal Sprague-Dawley (S-D) ratsdemonstrated shrinking of the prostate and reduction inepithelial cells upon C membranaceus administration [19]Further to this BPH models (S-D rats) also demonstratedprostate volume and prostatic index reduction in C mem-branaceus treated rats alongside a finasteride positive control[16 20] Having obtained positive results in the aforemen-tioned studies it was incumbent to further demonstrateevidence of effectiveness to back anecdotal claims

Improvement of urinary symptoms and QoL are impor-tant issues for decision making in the management of BPHClinical symptoms of BPH can be categorized into obstruc-tive or irritative symptoms The former is associated with thenarrowing of the prostatic urethra with subsequent difficultyin passing urine or weak or trickling stream of urine whilethe latter relates to sensation of incomplete bladder emptyingurgency nocturia and pollakiuria Both categories affect theQoL IPSS is a patientrsquos assessment index used to rank severityof symptoms and QoL [21]

The IPSS questionnaire has been used extensively inmany phytotherapeutic studies Some polyherbal productshave been documented to improve IPSS Chimaphila umbel-lata Populus tremula Pulsatilla pratensis Equisetum arvenseTriticumaestivum [22] andChimaphila umbellata (L) BartonPopulus tremula Pulsatilla pratensis (L) Mill Equisetumarvense L and Triticum aestivum L [23] are made up of5 polyherbal plants Others like Serenoa repens (Bartram)SmallUrtica dioica L are biherbal preparations [24 25]Both the polyherbal and biherbal preparations have beendocumented to reduced IPSS A few monoherbal plants havereduced IPSS These include Serenoa repens Bartram [34]Urtica dioica L [27] and Pteris multifida [28] In the presentstudy C membranaceus ethanolic root extract (a monoherbalpreparation) showed a significant reduction in total IPSS ofthe subjects at the end of the study period (119875 = 0001)Furthermore QoL improved significantly (119875 = 0001)Admittedly BPH symptoms impeach onQoL of subjectsThisimprovement was not age related (Figure 7) Additionallya significant change in QoL was noticed Although otherfactors in the IPSS questionnaire such as erectile functionsexual desire and overall satisfaction improved changeswerenot significant However overall satisfaction was significantlyhigher in younger men and age differences did not existafter treatment On the down side orgasmic function andoverall intercourse satisfaction were slightly worse (Table 1)Intercourse satisfaction is perhaps an age related perceptionas older men showed less satisfaction before treatment thanyounger men However some degree of improvement seenwas largely due to the reduction in severe dysfunction relatedto intercourse (Figure 9) It appears that C membranaceusprimarily targets only the prostate without adverse effectson sexual function This is of interest since 5-120572-reductaseinhibitors and 120572-1-adrenoceptor blockers affect erectile func-tion The improved QoL and IPSS may largely thereforebe related to relief of symptoms It is worthy to note thatsexual desire after treatment was almost significant Thiswill need further investigations to determine whether Cmembranaceus possess some aphrodisiac properties

Severe ED however dropped after treatment (Figure 6)Further support to this is the fact that severe lower urinarytract symptoms (LUTS) disappeared after 3 months with acorresponding increase in those with mild and moderatesymptoms (Figure 6) The improvement could be attributedto improved urination although such directly related param-eters were not measured Vacciniummacrocarpon Aiton is anexample of a monoherbal plant that demonstrated improvedLUTS after administration of its extract [29] Further evi-dence of improved IPSS is accompanied by reduced PSA

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

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Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 4: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

4 Evidence-Based Complementary and Alternative Medicine

7

12

11

13

17

0

0 2 4 6 8 10 12 14 16 18

TIPSS 2TIPSS 1

Severelysymptomatic

Moderatelysymptomatic

Mildlysymptomatic

Figure 1 A diagram showing the prostate symptom score (IPSS)before and after 3 months of plant extract administration

Age (yrs)0 20 40 60 80 100

0

2

4

6

8

QL before

Qua

lity

of li

fe

QL after

Figure 2 A relationship between age and QoL before (b) and after(a) treatment 119903 (b) = minus0010 119903 (a) = minus0330 and 119875 value (b) = 0956119875 value (a) = 0075

Table 1 Table showing prostate symptom score sexual functionand quality of life in BPH patients after three (3) months of Cmembranaceus ethanolic root extract administration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Age (yrs) 660 plusmn 110Total IPSS 151 plusmn 87 103 plusmn 47 0001lowast

Erectile function 100 plusmn 60 97 plusmn 41 0751Orgasmic function 26 plusmn 25 29 plusmn 24 0620Sexual desire 59 plusmn 25 50 plusmn 21 0053Intercourse satisfaction 38 plusmn 32 46 plusmn 25 0154Overall satisfaction 52 plusmn 36 48 plusmn 29 0598Quality of life 33 plusmn 16 17 plusmn 09 0001lowastlowastSignificance at 95 confidence interval

33 IIED Thirty percent (30) of the patients had severeerectile dysfunction 40 moderate dysfunction 24 mild-moderate dysfunction 3 mild dysfunction and 3 nodysfunction before treatment After treatment 20 of the

Age (yrs)0 20 40 60 80 100

0

10

20

30

Total IPSS before

Tota

l IPS

S

Total IPSS after

Figure 3 A relationship between age and IPSS before (b) and after(a) treatment 119903 (b) = 0005 119903 (a) = 0247 and 119875 value (b) = 0981 119875value (a) = 0189

IPSS before

TPSA

bef

ore

0 10 20 300

50

100

150

Figure 4 A correlation between tPSA and IPSS before treatment119903 = minus0089 119875 value = 0640

patients had severe erectile dysfunction 43 moderateand 37 mild-moderate dysfunction No patient had milddysfunction or no dysfunction after treatment

With regard to orgasmic dysfunction 53 had severeorgasmic dysfunction 27moderate 13mild-moderate 4mild and 3 no dysfunction before treatment After treat-ment 37 had severe orgasmic dysfunction 57 moderate3 mild-moderate 0 mild and 3 no dysfunction

Patients with severe dysfunction in sexual desire formed6 Twenty percent (20) 37 27 and 10 hadmoderatemild-moderate mild and no dysfunction in sexual desirerespectively before treatment compared to 10 severe 27moderate 50 mild-moderate 6 mild and 7 no dys-function after treatment Additionally 40 of the patientshad severe dysfunction 33 moderate 24 mild-moderate3 mild and 0 no dysfunction in intercourse satisfactionbefore treatment After treatment 23 had severe dysfunc-tion 67moderate 7mild-moderate 3mild dysfunctionand 0 no dysfunction

Evidence-Based Complementary and Alternative Medicine 5

0 5 10 15 200

20

40

60

IPSS after

TPSA

after

Figure 5 A correlation between tPSA and IPSS after treatment 119903 =minus221 119875 value = 0239

With the patientrsquos assessment on overall sexual satis-faction 27 had a severe dysfunction whilst 17 1723 and 16 of the rest of the patients had moderatemild-moderate mild and no dysfunction after treatmentSevere ED decreased with an increase in moderate symp-toms (Figure 6) Furthermore severe orgasmic dysfunctiondecreased after treatment with an increase in moderatedysfunction With regard to sexual desire mild to moder-ate dysfunction increased after treatment Severe and mildto moderate intercourse satisfaction dysfunction decreasedwhile moderate dysfunction increased Severe dysfunctionof overall satisfaction decreased with an increase in mildand no dysfunction (Figure 6) Furthermore there was asignificant positive association between the QoL and IPSSbefore treatment (119875 = 0002) (Figure 7) IPSS decreased aftertreatment with stable QoL (Figure 8)

In terms of age as age increased overall satisfactionwith ldquoprostate healthrdquo decreased This correlation howeverno longer existed after treatment (Figure 8) Correlationbetween ED and age indicated that ED was no longer age-dependent after treatment and had improved (Figure 9)Other insignificant associations with age occurred for sexualdesire intercourse satisfaction However overall satisfactionwhich was significantly age-dependent before treatment wasno longer a factor after treatment (Figure 10)

34 Biochemical Results

341 Routine Examinations From Table 2 RFT remainedrelatively unchanged after the 3-month study All LFTparameters increased slightly except for ALP that decreasedslightly but insignificantly However significant increaseswere observed in TBIL and IND BIL (119875 = 0001 119875 =0001 resp) (Table 3) The lipid profile remained virtuallyunchanged except forAPOA that increased significantly (119875 =0025) (Table 4)

342 Special Examinations From Table 5 total PSA (tPSA)reduced significantly from 279 plusmn 190 to 162 plusmn 118 ngmL

Table 2 A table showing renal function test (RFT) before and three(3) months after administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Sodium (mmolL) 1428 plusmn 66 1422 plusmn 66 0672Potassium (mmolL) 43 plusmn 06 43 plusmn 06 0609Urea (mmolL) 43 plusmn 14 44 plusmn 13 0664Creatinine (120583molL) 1059 plusmn 265 1060 plusmn 262 0981

Table 3 A table showing liver function test (LFT) before andthree (3) months after C membranaceus ethanolic root extractadministration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

AST (UL) 178 plusmn 44 186 plusmn 51 0391ALT (UL) 169 plusmn 65 179 plusmn 57 0465GGT (UL) 349 plusmn 153 358 plusmn 192 0729ALP (UL) 766 plusmn 523 688 plusmn 206 0441TP (gL) 744 plusmn 69 753 plusmn 90 0495ALB (gL) 442 plusmn 48 460 plusmn 72 0092TBIL (120583molL) 49 plusmn 26 83 plusmn 47 0001lowast

DBIL (120583molL) 29 plusmn 22 34 plusmn 25 0347IND BIL (120583molL) 20 plusmn 18 48 plusmn 45 0001lowastlowastSignificance at 95 confidence interval

Table 4 A table showing serum lipid levels before and three (3)months after C membranaceus ethanolic root extract administra-tion at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

TC (mmolL) 503 plusmn 112 519 plusmn 115 0423TG (mmolL) 115 plusmn 043 122 plusmn 056 0518HDL (mmolL) 076 plusmn 033 088 plusmn 032 0063LDL (mmolL) 374 plusmn 103 375 plusmn 102 0959APO A (gL) 131 plusmn 045 151 plusmn 047 0025lowast

APO B (gL) 058 plusmn 037 049 plusmn 013 0222APO BA ratio 281 plusmn 147 324 plusmn 127 0067lowastSignificance at 95 confidence interval

(119875 = 0002) Furthermore free PSA (fPSA) reduced from61 plusmn 48 to 39 plusmn 29ngmL (119875 = 0045) However PSA ratiodid not significantly change

35 Abdominopelvic Scan Data from the abdominopelvicscan showed that mean prostate volume reduced from 1018plusmn413 to 545 plusmn 248 cm3 The change over the 3-month periodwas significant (119875 = 0023)

6 Evidence-Based Complementary and Alternative Medicine

Erectile function before

Erectile function after

Orgasmic function before

Orgasmic function after

Sexual desire before

Sexual desire after

Intercourse sat before

Intercourse sat after

Overall sat before

Overall sat after

0 5 10 15 20 25

IIEF

Number of patients

No dysfunctionMild dysfunction Mild to moderate

Moderate dysfunction

Severe dysfunction dysfunction

Figure 6 A diagram showing the general overview of patientrsquos condition before and after treatment using the IIEF questionnaire

IPSS before

QL

befo

re

0 10 20 300

2

4

6

8

Figure 7 A correlation between QoL and IPSS before treatmentQoL before treatment strongly depended on IPSS 119903 = 0634119875 value= 0002

Table 5 Table showing the different levels of total PSA (tPSA) freePSA (fPSA) PSA ratio and prostate volume before and after three(3) months of administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

Total PSA (ngmL) 274 plusmn 190 162 plusmn 118 0002lowast

Free PSA (ngmL) 61 plusmn 48 39 plusmn 29 0045lowast

PSA ratio () 239 plusmn 187 246 plusmn 164 0813Prostate volume (cm3) 1018 plusmn 413 545 plusmn 248 0023lowastlowastSignificance at 95 confidence interval

0 5 10 15 200

1

2

3

4

IPSS after

QL

after

Figure 8 A correlation betweenQoL and IPSS after treatment QoLappear to be stable and not dependent on IPSS 119903 = 0061 and 119875 =0747

4 Discussion

BPH continues to be a major problem worldwide Whilenew pharmaceutical drugs are being sought for a gradualbut substantive shift to nutraceuticals and medicinal plantsis occurring globally Medicinal plants are being used by80 of the worldrsquos population In emerging economies itis the first line of medical support Nonetheless in someadvanced economies like Germany and Austria 90 usephytotherapeutic agents [7] The drive towards the use ofphytotherapeutic agents is a decision based on safety and sideeffects Mostmedicinal plants have been used for ages and areconsidered safe with fewer side effects

Evidence-Based Complementary and Alternative Medicine 7

Age (yrs)0 20 40 60 80 100

0

5

10

15

Orgasmic fxn before

Org

asm

ic fu

nctio

n

Orgasmic fxn after

Figure 9 A relationship between age and orgasmic function before(b) and after (a) treatment Orgasmic function remained relativelyunchanged Before 119903 = minus0179 119875 = 0344 after 119903 = minus0303 119875 =0103

Age (yrs)0 20 40 60 80 100

0

5

10

15

Ove

rall

satis

fact

ion

Overall sat beforeOverall sat after

Figure 10 A relationship between age and the overall patientsatisfaction before (b) and after (a) treatment Overall satisfactionwas determined by age before treatmentThis no longer existed aftertreatment Overall satisfaction appears to have stabilized Before119903 = minus0364 119875 = 0048 and after 119903 = 0024 119875 = 0901

C membranaceus aqueous root extract has been used inGhana for decades for BPH treatment The last decade hashowever witnessed a surge in scientific data on the effect ofC membranaceus in vitro and in vivo (animal studies)

Animal studies using normal Sprague-Dawley (S-D) ratsdemonstrated shrinking of the prostate and reduction inepithelial cells upon C membranaceus administration [19]Further to this BPH models (S-D rats) also demonstratedprostate volume and prostatic index reduction in C mem-branaceus treated rats alongside a finasteride positive control[16 20] Having obtained positive results in the aforemen-tioned studies it was incumbent to further demonstrateevidence of effectiveness to back anecdotal claims

Improvement of urinary symptoms and QoL are impor-tant issues for decision making in the management of BPHClinical symptoms of BPH can be categorized into obstruc-tive or irritative symptoms The former is associated with thenarrowing of the prostatic urethra with subsequent difficultyin passing urine or weak or trickling stream of urine whilethe latter relates to sensation of incomplete bladder emptyingurgency nocturia and pollakiuria Both categories affect theQoL IPSS is a patientrsquos assessment index used to rank severityof symptoms and QoL [21]

The IPSS questionnaire has been used extensively inmany phytotherapeutic studies Some polyherbal productshave been documented to improve IPSS Chimaphila umbel-lata Populus tremula Pulsatilla pratensis Equisetum arvenseTriticumaestivum [22] andChimaphila umbellata (L) BartonPopulus tremula Pulsatilla pratensis (L) Mill Equisetumarvense L and Triticum aestivum L [23] are made up of5 polyherbal plants Others like Serenoa repens (Bartram)SmallUrtica dioica L are biherbal preparations [24 25]Both the polyherbal and biherbal preparations have beendocumented to reduced IPSS A few monoherbal plants havereduced IPSS These include Serenoa repens Bartram [34]Urtica dioica L [27] and Pteris multifida [28] In the presentstudy C membranaceus ethanolic root extract (a monoherbalpreparation) showed a significant reduction in total IPSS ofthe subjects at the end of the study period (119875 = 0001)Furthermore QoL improved significantly (119875 = 0001)Admittedly BPH symptoms impeach onQoL of subjectsThisimprovement was not age related (Figure 7) Additionallya significant change in QoL was noticed Although otherfactors in the IPSS questionnaire such as erectile functionsexual desire and overall satisfaction improved changeswerenot significant However overall satisfaction was significantlyhigher in younger men and age differences did not existafter treatment On the down side orgasmic function andoverall intercourse satisfaction were slightly worse (Table 1)Intercourse satisfaction is perhaps an age related perceptionas older men showed less satisfaction before treatment thanyounger men However some degree of improvement seenwas largely due to the reduction in severe dysfunction relatedto intercourse (Figure 9) It appears that C membranaceusprimarily targets only the prostate without adverse effectson sexual function This is of interest since 5-120572-reductaseinhibitors and 120572-1-adrenoceptor blockers affect erectile func-tion The improved QoL and IPSS may largely thereforebe related to relief of symptoms It is worthy to note thatsexual desire after treatment was almost significant Thiswill need further investigations to determine whether Cmembranaceus possess some aphrodisiac properties

Severe ED however dropped after treatment (Figure 6)Further support to this is the fact that severe lower urinarytract symptoms (LUTS) disappeared after 3 months with acorresponding increase in those with mild and moderatesymptoms (Figure 6) The improvement could be attributedto improved urination although such directly related param-eters were not measured Vacciniummacrocarpon Aiton is anexample of a monoherbal plant that demonstrated improvedLUTS after administration of its extract [29] Further evi-dence of improved IPSS is accompanied by reduced PSA

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

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Disease Markers

Hindawiwwwhindawicom Volume 2018

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

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Hindawiwwwhindawicom Volume 2018

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Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 5: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

Evidence-Based Complementary and Alternative Medicine 5

0 5 10 15 200

20

40

60

IPSS after

TPSA

after

Figure 5 A correlation between tPSA and IPSS after treatment 119903 =minus221 119875 value = 0239

With the patientrsquos assessment on overall sexual satis-faction 27 had a severe dysfunction whilst 17 1723 and 16 of the rest of the patients had moderatemild-moderate mild and no dysfunction after treatmentSevere ED decreased with an increase in moderate symp-toms (Figure 6) Furthermore severe orgasmic dysfunctiondecreased after treatment with an increase in moderatedysfunction With regard to sexual desire mild to moder-ate dysfunction increased after treatment Severe and mildto moderate intercourse satisfaction dysfunction decreasedwhile moderate dysfunction increased Severe dysfunctionof overall satisfaction decreased with an increase in mildand no dysfunction (Figure 6) Furthermore there was asignificant positive association between the QoL and IPSSbefore treatment (119875 = 0002) (Figure 7) IPSS decreased aftertreatment with stable QoL (Figure 8)

In terms of age as age increased overall satisfactionwith ldquoprostate healthrdquo decreased This correlation howeverno longer existed after treatment (Figure 8) Correlationbetween ED and age indicated that ED was no longer age-dependent after treatment and had improved (Figure 9)Other insignificant associations with age occurred for sexualdesire intercourse satisfaction However overall satisfactionwhich was significantly age-dependent before treatment wasno longer a factor after treatment (Figure 10)

34 Biochemical Results

341 Routine Examinations From Table 2 RFT remainedrelatively unchanged after the 3-month study All LFTparameters increased slightly except for ALP that decreasedslightly but insignificantly However significant increaseswere observed in TBIL and IND BIL (119875 = 0001 119875 =0001 resp) (Table 3) The lipid profile remained virtuallyunchanged except forAPOA that increased significantly (119875 =0025) (Table 4)

342 Special Examinations From Table 5 total PSA (tPSA)reduced significantly from 279 plusmn 190 to 162 plusmn 118 ngmL

Table 2 A table showing renal function test (RFT) before and three(3) months after administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

Sodium (mmolL) 1428 plusmn 66 1422 plusmn 66 0672Potassium (mmolL) 43 plusmn 06 43 plusmn 06 0609Urea (mmolL) 43 plusmn 14 44 plusmn 13 0664Creatinine (120583molL) 1059 plusmn 265 1060 plusmn 262 0981

Table 3 A table showing liver function test (LFT) before andthree (3) months after C membranaceus ethanolic root extractadministration at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after) 119875 value

AST (UL) 178 plusmn 44 186 plusmn 51 0391ALT (UL) 169 plusmn 65 179 plusmn 57 0465GGT (UL) 349 plusmn 153 358 plusmn 192 0729ALP (UL) 766 plusmn 523 688 plusmn 206 0441TP (gL) 744 plusmn 69 753 plusmn 90 0495ALB (gL) 442 plusmn 48 460 plusmn 72 0092TBIL (120583molL) 49 plusmn 26 83 plusmn 47 0001lowast

DBIL (120583molL) 29 plusmn 22 34 plusmn 25 0347IND BIL (120583molL) 20 plusmn 18 48 plusmn 45 0001lowastlowastSignificance at 95 confidence interval

Table 4 A table showing serum lipid levels before and three (3)months after C membranaceus ethanolic root extract administra-tion at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

TC (mmolL) 503 plusmn 112 519 plusmn 115 0423TG (mmolL) 115 plusmn 043 122 plusmn 056 0518HDL (mmolL) 076 plusmn 033 088 plusmn 032 0063LDL (mmolL) 374 plusmn 103 375 plusmn 102 0959APO A (gL) 131 plusmn 045 151 plusmn 047 0025lowast

APO B (gL) 058 plusmn 037 049 plusmn 013 0222APO BA ratio 281 plusmn 147 324 plusmn 127 0067lowastSignificance at 95 confidence interval

(119875 = 0002) Furthermore free PSA (fPSA) reduced from61 plusmn 48 to 39 plusmn 29ngmL (119875 = 0045) However PSA ratiodid not significantly change

35 Abdominopelvic Scan Data from the abdominopelvicscan showed that mean prostate volume reduced from 1018plusmn413 to 545 plusmn 248 cm3 The change over the 3-month periodwas significant (119875 = 0023)

6 Evidence-Based Complementary and Alternative Medicine

Erectile function before

Erectile function after

Orgasmic function before

Orgasmic function after

Sexual desire before

Sexual desire after

Intercourse sat before

Intercourse sat after

Overall sat before

Overall sat after

0 5 10 15 20 25

IIEF

Number of patients

No dysfunctionMild dysfunction Mild to moderate

Moderate dysfunction

Severe dysfunction dysfunction

Figure 6 A diagram showing the general overview of patientrsquos condition before and after treatment using the IIEF questionnaire

IPSS before

QL

befo

re

0 10 20 300

2

4

6

8

Figure 7 A correlation between QoL and IPSS before treatmentQoL before treatment strongly depended on IPSS 119903 = 0634119875 value= 0002

Table 5 Table showing the different levels of total PSA (tPSA) freePSA (fPSA) PSA ratio and prostate volume before and after three(3) months of administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

Total PSA (ngmL) 274 plusmn 190 162 plusmn 118 0002lowast

Free PSA (ngmL) 61 plusmn 48 39 plusmn 29 0045lowast

PSA ratio () 239 plusmn 187 246 plusmn 164 0813Prostate volume (cm3) 1018 plusmn 413 545 plusmn 248 0023lowastlowastSignificance at 95 confidence interval

0 5 10 15 200

1

2

3

4

IPSS after

QL

after

Figure 8 A correlation betweenQoL and IPSS after treatment QoLappear to be stable and not dependent on IPSS 119903 = 0061 and 119875 =0747

4 Discussion

BPH continues to be a major problem worldwide Whilenew pharmaceutical drugs are being sought for a gradualbut substantive shift to nutraceuticals and medicinal plantsis occurring globally Medicinal plants are being used by80 of the worldrsquos population In emerging economies itis the first line of medical support Nonetheless in someadvanced economies like Germany and Austria 90 usephytotherapeutic agents [7] The drive towards the use ofphytotherapeutic agents is a decision based on safety and sideeffects Mostmedicinal plants have been used for ages and areconsidered safe with fewer side effects

Evidence-Based Complementary and Alternative Medicine 7

Age (yrs)0 20 40 60 80 100

0

5

10

15

Orgasmic fxn before

Org

asm

ic fu

nctio

n

Orgasmic fxn after

Figure 9 A relationship between age and orgasmic function before(b) and after (a) treatment Orgasmic function remained relativelyunchanged Before 119903 = minus0179 119875 = 0344 after 119903 = minus0303 119875 =0103

Age (yrs)0 20 40 60 80 100

0

5

10

15

Ove

rall

satis

fact

ion

Overall sat beforeOverall sat after

Figure 10 A relationship between age and the overall patientsatisfaction before (b) and after (a) treatment Overall satisfactionwas determined by age before treatmentThis no longer existed aftertreatment Overall satisfaction appears to have stabilized Before119903 = minus0364 119875 = 0048 and after 119903 = 0024 119875 = 0901

C membranaceus aqueous root extract has been used inGhana for decades for BPH treatment The last decade hashowever witnessed a surge in scientific data on the effect ofC membranaceus in vitro and in vivo (animal studies)

Animal studies using normal Sprague-Dawley (S-D) ratsdemonstrated shrinking of the prostate and reduction inepithelial cells upon C membranaceus administration [19]Further to this BPH models (S-D rats) also demonstratedprostate volume and prostatic index reduction in C mem-branaceus treated rats alongside a finasteride positive control[16 20] Having obtained positive results in the aforemen-tioned studies it was incumbent to further demonstrateevidence of effectiveness to back anecdotal claims

Improvement of urinary symptoms and QoL are impor-tant issues for decision making in the management of BPHClinical symptoms of BPH can be categorized into obstruc-tive or irritative symptoms The former is associated with thenarrowing of the prostatic urethra with subsequent difficultyin passing urine or weak or trickling stream of urine whilethe latter relates to sensation of incomplete bladder emptyingurgency nocturia and pollakiuria Both categories affect theQoL IPSS is a patientrsquos assessment index used to rank severityof symptoms and QoL [21]

The IPSS questionnaire has been used extensively inmany phytotherapeutic studies Some polyherbal productshave been documented to improve IPSS Chimaphila umbel-lata Populus tremula Pulsatilla pratensis Equisetum arvenseTriticumaestivum [22] andChimaphila umbellata (L) BartonPopulus tremula Pulsatilla pratensis (L) Mill Equisetumarvense L and Triticum aestivum L [23] are made up of5 polyherbal plants Others like Serenoa repens (Bartram)SmallUrtica dioica L are biherbal preparations [24 25]Both the polyherbal and biherbal preparations have beendocumented to reduced IPSS A few monoherbal plants havereduced IPSS These include Serenoa repens Bartram [34]Urtica dioica L [27] and Pteris multifida [28] In the presentstudy C membranaceus ethanolic root extract (a monoherbalpreparation) showed a significant reduction in total IPSS ofthe subjects at the end of the study period (119875 = 0001)Furthermore QoL improved significantly (119875 = 0001)Admittedly BPH symptoms impeach onQoL of subjectsThisimprovement was not age related (Figure 7) Additionallya significant change in QoL was noticed Although otherfactors in the IPSS questionnaire such as erectile functionsexual desire and overall satisfaction improved changeswerenot significant However overall satisfaction was significantlyhigher in younger men and age differences did not existafter treatment On the down side orgasmic function andoverall intercourse satisfaction were slightly worse (Table 1)Intercourse satisfaction is perhaps an age related perceptionas older men showed less satisfaction before treatment thanyounger men However some degree of improvement seenwas largely due to the reduction in severe dysfunction relatedto intercourse (Figure 9) It appears that C membranaceusprimarily targets only the prostate without adverse effectson sexual function This is of interest since 5-120572-reductaseinhibitors and 120572-1-adrenoceptor blockers affect erectile func-tion The improved QoL and IPSS may largely thereforebe related to relief of symptoms It is worthy to note thatsexual desire after treatment was almost significant Thiswill need further investigations to determine whether Cmembranaceus possess some aphrodisiac properties

Severe ED however dropped after treatment (Figure 6)Further support to this is the fact that severe lower urinarytract symptoms (LUTS) disappeared after 3 months with acorresponding increase in those with mild and moderatesymptoms (Figure 6) The improvement could be attributedto improved urination although such directly related param-eters were not measured Vacciniummacrocarpon Aiton is anexample of a monoherbal plant that demonstrated improvedLUTS after administration of its extract [29] Further evi-dence of improved IPSS is accompanied by reduced PSA

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

Stem Cells International

Hindawiwwwhindawicom Volume 2018

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MEDIATORSINFLAMMATION

of

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Hindawiwwwhindawicom Volume 2018

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Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

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Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

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Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

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OphthalmologyJournal of

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Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

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Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 6: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

6 Evidence-Based Complementary and Alternative Medicine

Erectile function before

Erectile function after

Orgasmic function before

Orgasmic function after

Sexual desire before

Sexual desire after

Intercourse sat before

Intercourse sat after

Overall sat before

Overall sat after

0 5 10 15 20 25

IIEF

Number of patients

No dysfunctionMild dysfunction Mild to moderate

Moderate dysfunction

Severe dysfunction dysfunction

Figure 6 A diagram showing the general overview of patientrsquos condition before and after treatment using the IIEF questionnaire

IPSS before

QL

befo

re

0 10 20 300

2

4

6

8

Figure 7 A correlation between QoL and IPSS before treatmentQoL before treatment strongly depended on IPSS 119903 = 0634119875 value= 0002

Table 5 Table showing the different levels of total PSA (tPSA) freePSA (fPSA) PSA ratio and prostate volume before and after three(3) months of administration of C membranaceus ethanolic rootextract at 20mg tid

Parameter Mean plusmn SD(before)

Mean plusmn SD(after)

119875 value

Total PSA (ngmL) 274 plusmn 190 162 plusmn 118 0002lowast

Free PSA (ngmL) 61 plusmn 48 39 plusmn 29 0045lowast

PSA ratio () 239 plusmn 187 246 plusmn 164 0813Prostate volume (cm3) 1018 plusmn 413 545 plusmn 248 0023lowastlowastSignificance at 95 confidence interval

0 5 10 15 200

1

2

3

4

IPSS after

QL

after

Figure 8 A correlation betweenQoL and IPSS after treatment QoLappear to be stable and not dependent on IPSS 119903 = 0061 and 119875 =0747

4 Discussion

BPH continues to be a major problem worldwide Whilenew pharmaceutical drugs are being sought for a gradualbut substantive shift to nutraceuticals and medicinal plantsis occurring globally Medicinal plants are being used by80 of the worldrsquos population In emerging economies itis the first line of medical support Nonetheless in someadvanced economies like Germany and Austria 90 usephytotherapeutic agents [7] The drive towards the use ofphytotherapeutic agents is a decision based on safety and sideeffects Mostmedicinal plants have been used for ages and areconsidered safe with fewer side effects

Evidence-Based Complementary and Alternative Medicine 7

Age (yrs)0 20 40 60 80 100

0

5

10

15

Orgasmic fxn before

Org

asm

ic fu

nctio

n

Orgasmic fxn after

Figure 9 A relationship between age and orgasmic function before(b) and after (a) treatment Orgasmic function remained relativelyunchanged Before 119903 = minus0179 119875 = 0344 after 119903 = minus0303 119875 =0103

Age (yrs)0 20 40 60 80 100

0

5

10

15

Ove

rall

satis

fact

ion

Overall sat beforeOverall sat after

Figure 10 A relationship between age and the overall patientsatisfaction before (b) and after (a) treatment Overall satisfactionwas determined by age before treatmentThis no longer existed aftertreatment Overall satisfaction appears to have stabilized Before119903 = minus0364 119875 = 0048 and after 119903 = 0024 119875 = 0901

C membranaceus aqueous root extract has been used inGhana for decades for BPH treatment The last decade hashowever witnessed a surge in scientific data on the effect ofC membranaceus in vitro and in vivo (animal studies)

Animal studies using normal Sprague-Dawley (S-D) ratsdemonstrated shrinking of the prostate and reduction inepithelial cells upon C membranaceus administration [19]Further to this BPH models (S-D rats) also demonstratedprostate volume and prostatic index reduction in C mem-branaceus treated rats alongside a finasteride positive control[16 20] Having obtained positive results in the aforemen-tioned studies it was incumbent to further demonstrateevidence of effectiveness to back anecdotal claims

Improvement of urinary symptoms and QoL are impor-tant issues for decision making in the management of BPHClinical symptoms of BPH can be categorized into obstruc-tive or irritative symptoms The former is associated with thenarrowing of the prostatic urethra with subsequent difficultyin passing urine or weak or trickling stream of urine whilethe latter relates to sensation of incomplete bladder emptyingurgency nocturia and pollakiuria Both categories affect theQoL IPSS is a patientrsquos assessment index used to rank severityof symptoms and QoL [21]

The IPSS questionnaire has been used extensively inmany phytotherapeutic studies Some polyherbal productshave been documented to improve IPSS Chimaphila umbel-lata Populus tremula Pulsatilla pratensis Equisetum arvenseTriticumaestivum [22] andChimaphila umbellata (L) BartonPopulus tremula Pulsatilla pratensis (L) Mill Equisetumarvense L and Triticum aestivum L [23] are made up of5 polyherbal plants Others like Serenoa repens (Bartram)SmallUrtica dioica L are biherbal preparations [24 25]Both the polyherbal and biherbal preparations have beendocumented to reduced IPSS A few monoherbal plants havereduced IPSS These include Serenoa repens Bartram [34]Urtica dioica L [27] and Pteris multifida [28] In the presentstudy C membranaceus ethanolic root extract (a monoherbalpreparation) showed a significant reduction in total IPSS ofthe subjects at the end of the study period (119875 = 0001)Furthermore QoL improved significantly (119875 = 0001)Admittedly BPH symptoms impeach onQoL of subjectsThisimprovement was not age related (Figure 7) Additionallya significant change in QoL was noticed Although otherfactors in the IPSS questionnaire such as erectile functionsexual desire and overall satisfaction improved changeswerenot significant However overall satisfaction was significantlyhigher in younger men and age differences did not existafter treatment On the down side orgasmic function andoverall intercourse satisfaction were slightly worse (Table 1)Intercourse satisfaction is perhaps an age related perceptionas older men showed less satisfaction before treatment thanyounger men However some degree of improvement seenwas largely due to the reduction in severe dysfunction relatedto intercourse (Figure 9) It appears that C membranaceusprimarily targets only the prostate without adverse effectson sexual function This is of interest since 5-120572-reductaseinhibitors and 120572-1-adrenoceptor blockers affect erectile func-tion The improved QoL and IPSS may largely thereforebe related to relief of symptoms It is worthy to note thatsexual desire after treatment was almost significant Thiswill need further investigations to determine whether Cmembranaceus possess some aphrodisiac properties

Severe ED however dropped after treatment (Figure 6)Further support to this is the fact that severe lower urinarytract symptoms (LUTS) disappeared after 3 months with acorresponding increase in those with mild and moderatesymptoms (Figure 6) The improvement could be attributedto improved urination although such directly related param-eters were not measured Vacciniummacrocarpon Aiton is anexample of a monoherbal plant that demonstrated improvedLUTS after administration of its extract [29] Further evi-dence of improved IPSS is accompanied by reduced PSA

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 7: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

Evidence-Based Complementary and Alternative Medicine 7

Age (yrs)0 20 40 60 80 100

0

5

10

15

Orgasmic fxn before

Org

asm

ic fu

nctio

n

Orgasmic fxn after

Figure 9 A relationship between age and orgasmic function before(b) and after (a) treatment Orgasmic function remained relativelyunchanged Before 119903 = minus0179 119875 = 0344 after 119903 = minus0303 119875 =0103

Age (yrs)0 20 40 60 80 100

0

5

10

15

Ove

rall

satis

fact

ion

Overall sat beforeOverall sat after

Figure 10 A relationship between age and the overall patientsatisfaction before (b) and after (a) treatment Overall satisfactionwas determined by age before treatmentThis no longer existed aftertreatment Overall satisfaction appears to have stabilized Before119903 = minus0364 119875 = 0048 and after 119903 = 0024 119875 = 0901

C membranaceus aqueous root extract has been used inGhana for decades for BPH treatment The last decade hashowever witnessed a surge in scientific data on the effect ofC membranaceus in vitro and in vivo (animal studies)

Animal studies using normal Sprague-Dawley (S-D) ratsdemonstrated shrinking of the prostate and reduction inepithelial cells upon C membranaceus administration [19]Further to this BPH models (S-D rats) also demonstratedprostate volume and prostatic index reduction in C mem-branaceus treated rats alongside a finasteride positive control[16 20] Having obtained positive results in the aforemen-tioned studies it was incumbent to further demonstrateevidence of effectiveness to back anecdotal claims

Improvement of urinary symptoms and QoL are impor-tant issues for decision making in the management of BPHClinical symptoms of BPH can be categorized into obstruc-tive or irritative symptoms The former is associated with thenarrowing of the prostatic urethra with subsequent difficultyin passing urine or weak or trickling stream of urine whilethe latter relates to sensation of incomplete bladder emptyingurgency nocturia and pollakiuria Both categories affect theQoL IPSS is a patientrsquos assessment index used to rank severityof symptoms and QoL [21]

The IPSS questionnaire has been used extensively inmany phytotherapeutic studies Some polyherbal productshave been documented to improve IPSS Chimaphila umbel-lata Populus tremula Pulsatilla pratensis Equisetum arvenseTriticumaestivum [22] andChimaphila umbellata (L) BartonPopulus tremula Pulsatilla pratensis (L) Mill Equisetumarvense L and Triticum aestivum L [23] are made up of5 polyherbal plants Others like Serenoa repens (Bartram)SmallUrtica dioica L are biherbal preparations [24 25]Both the polyherbal and biherbal preparations have beendocumented to reduced IPSS A few monoherbal plants havereduced IPSS These include Serenoa repens Bartram [34]Urtica dioica L [27] and Pteris multifida [28] In the presentstudy C membranaceus ethanolic root extract (a monoherbalpreparation) showed a significant reduction in total IPSS ofthe subjects at the end of the study period (119875 = 0001)Furthermore QoL improved significantly (119875 = 0001)Admittedly BPH symptoms impeach onQoL of subjectsThisimprovement was not age related (Figure 7) Additionallya significant change in QoL was noticed Although otherfactors in the IPSS questionnaire such as erectile functionsexual desire and overall satisfaction improved changeswerenot significant However overall satisfaction was significantlyhigher in younger men and age differences did not existafter treatment On the down side orgasmic function andoverall intercourse satisfaction were slightly worse (Table 1)Intercourse satisfaction is perhaps an age related perceptionas older men showed less satisfaction before treatment thanyounger men However some degree of improvement seenwas largely due to the reduction in severe dysfunction relatedto intercourse (Figure 9) It appears that C membranaceusprimarily targets only the prostate without adverse effectson sexual function This is of interest since 5-120572-reductaseinhibitors and 120572-1-adrenoceptor blockers affect erectile func-tion The improved QoL and IPSS may largely thereforebe related to relief of symptoms It is worthy to note thatsexual desire after treatment was almost significant Thiswill need further investigations to determine whether Cmembranaceus possess some aphrodisiac properties

Severe ED however dropped after treatment (Figure 6)Further support to this is the fact that severe lower urinarytract symptoms (LUTS) disappeared after 3 months with acorresponding increase in those with mild and moderatesymptoms (Figure 6) The improvement could be attributedto improved urination although such directly related param-eters were not measured Vacciniummacrocarpon Aiton is anexample of a monoherbal plant that demonstrated improvedLUTS after administration of its extract [29] Further evi-dence of improved IPSS is accompanied by reduced PSA

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 8: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

8 Evidence-Based Complementary and Alternative Medicine

levels Most medicinal plant studies (in animals and humans)did not measure PSA after the treatment period HoweverEngelhardt and Riedl reported a significant decrease in IPSSand PSA after one-year isoflavone extract from red clover[30] This study also reports not only improved IPSS but alsosignificant reduction in both tPSA and fPSA (Table 2)

Total PSA is the sum of both bound and free PSA how-ever free PSA is assessed only if the total PSA is increasedPSA is primarily a tissue-specific marker From an elevatedPSA measurement it is difficult to distinguish between abenign and malignant transformation of the prostate glandDifferentiating between the two is where free PSA is usefulFree PSA is more often formed from benign transformationswhile boundPSA tends to come frommalign transformations[31] In this study both fPSA and tPSA were found to besignificant However the ratio was not significant before andafter treatment Collectively the free total PSA ratio canbe used as an additional marker for prognosis of hormonetreatment [32]

Total and indirect (unconjugated) bilirubin levels signif-icantly increased in this study However levels were withinthe normal reference interval Such physiological increasesare beneficial and bilirubin has been demonstrated to be aneffective antioxidant using isolated heart mitochondria [33]

Apolipoprotein A-I is the major protein component ofhigh density lipoprotein (HDL) in plasma Chylomicronssecreted from the intestinal enterocyte also contain apo A-I but it is quickly transferred to HDL in the bloodstream[34] The protein promotes fat efflux including cholesterolfrom tissues to the liver for excretion Apolipoprotein A-I itself also removes seeding molecules for oxidation fromthe arterial wall and also facilitates reverse cholesterol trans-port In this study Apo A was significantly elevated aftertreatment in tandem with an increase in HDL which wasalmost significant Hence C membranaceus appears to haveantiatherogenic properties as observed in preclinical studies[35]

Further clinical significance is the reduction in prostatevolume Indeed two hypotheses exist concerning the pathoe-tiology of BPH Prostate enlargement has been attributedto the accumulation of dihydrotestosterone (DHT) (whichmay cause cellular hyperplasia) and an increase in prostaticestrogen levels with age Reduced prostate volume andprostatic index have previously been shown with the useof C membranaceus aqueous root extract in animal models[17 19 35] Secale cereale in combination with Serenoarepens is said to reduce prostate volume in animals [36]Some studies using Cucurbita pepo L and Lepidium meyeniias monoherbal preparations documented reduced prostatevolume in animal models [37 38] Only few human studieswith phytomedicines have demonstrated prostate volumereduction In a meta-analysis by Azimi et al [39] 32 humanstudies involving the use of medicinal plants were docu-mented PR-2000 a polyherbal plant extract (made up ofTribulus terrestris L Caesalpinia bonducella (L) FlemingAsparagus racemosus Willd Areca catechu L and Crataevanurvala Buch-Ham) reduced prostate volume after 6 monthstreatment [21] Two monoherbal plants were said to haveshrank the prostate Of the two the study of Safarinejad

[40] reported mild shrinkage using Urtica dioica L extractThe other by Engelhardt and Riedl [30] used 60mgdayisoflavone from Trifolium pretense (red clover) on 20 BPHpatients and reported a reduction in prostate volume andPSAand improved IPSS In that study PSA reduced significantlyby 33 from 1016 ngmL to 715 ngmL In this study thePSA reduced significantly by 408 from 274 ngmL to162 ngmL Reduction of PSA observed in this study corrob-orates findings from preclinical studies [17] and this could beattributed to its possible 5120572-reductase inhibitory propertiesProstate volume shrinkage after 12-month treatment in thestudy of Debruyne et al [26] was modest and insignificant(493 cm3 to 443 cm3) Of more serious consequences inthat study is the fact that all three liver transaminasessignificantly increased (119875 lt 0001) at the end of the studysignifying commencement of liver damage In this studyprostate volume reduced significantly by 466 after 3-monthCmembranaceus administration (119875 = 0023) Liver functionrenal function tests and lipid profile remained normal

5 Conclusion

In conclusion the ethanolic root extract of C membranaceusis one of the few monoherbal products that remarkablyreduces PSA levels prostate volume and subsequentlyimproves the QoL of patients with BPH There is the needfor a larger multicentered clinical trial to further confirm itsefficacy and beneficial effects

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Funding for the study was provided by the Office of ResearchInnovation and Development (ORID) University of Ghana

References

[1] G C Roehrborn ldquoBenign prostatic hyperplasia an overviewrdquoReviews in Urology vol 7 supplement 9 pp S3ndashS14 2005

[2] N Dhingra and D Bhagwat ldquoBenign prostatic hyperplasia anoverview of existing treatmentrdquo Indian Journal of Pharmacol-ogy vol 43 no 1 pp 6ndash12 2011

[3] C Roehrborn ldquoBenign prostatic hyperplasia and lower urinarytract symptom guidelinesrdquo Canadian Urology Association Jour-nal vol 6 no 5 supplement 2 pp S130ndashS132 2012

[4] D M Eisenberg R B Davis S L Ettner et al ldquoTrends inalternativemedicine use in the United States 1990ndash1997 resultsof a follow-up national surveyrdquo The Journal of the AmericanMedical Association vol 280 no 18 pp 1569ndash1575 1998

[5] R C Rosen J T Wei S E Althof A D Seftel M Miner andM A Perelman ldquoAssociation of sexual dysfunction with lowerurinary tract symptoms of BPH and BPH medical therapiesresults from the BPH Registryrdquo Urology vol 73 no 3 pp 562ndash566 2009

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 9: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

Evidence-Based Complementary and Alternative Medicine 9

[6] S A Kaplan D E Chung R K Lee S Scofield and A E Te ldquoA5-year retrospective analysis of 5120572-reductase inhibitors in menwith benign prostatic hyperplasia finasteride has comparableurinary symptom efficacy and prostate volume reduction butless sexual side effects and breast complications than dutas-teriderdquo International Journal of Clinical Practice vol 66 no 11pp 1052ndash1055 2012

[7] L Zegarra A Vaisberg C Loza et al ldquoDouble-blind random-ized placebo-controlled study of Bixa orellana in patients withlower urinary tract symptoms associated to benign prostatichyperplasiardquo International Brazilian Journal of Urology vol 33no 4 pp 493ndash501 2007

[8] K Devesh and P K Mishra ldquoPlant based contraceptive popularamong tribals of Iharkhandrdquo Bioscience Discovery vol 2 no 1pp 11ndash14 2011

[9] J Yarney A Donkor S Y Opoku et al ldquoCharacteristics ofusers and implications for the use of complementary andalternative medicine in Ghanaian cancer patients undergoingradiotherapy and chemotherapy a cross- sectional studyrdquo BMCComplementary amp Alternative Medicine vol 13 article 16 2013

[10] A A Appiah W A Asomaning I V Oppong et al ldquoProspectsof Croton membranaceus for prostate health rdquo in AfricanNatural Plant Products Volume II Discoveries and Challengesin Chemistry Health and Nutrition H R Juliani J E Simonand C-T Ho Eds vol 1127 pp 79ndash92 Oxford University PressWashington DC USA 2013

[11] F A Aboagye The effect of Croton membranaceus on dihy-drotestosterone levels in blood and its synthesis by prostatic5 alpha-reductase in the rat [MPhil thesis] Department ofBiochemistry University of Ghana 1997

[12] F A Aboagye G H Sam G Massiot and C Lavaud ldquoJulocro-tine a glutarimide alkaloid from Croton membranaceusrdquoFitoterapia vol 71 no 4 pp 461ndash462 2000

[13] M Lambert D Staeligrk S H Hansen and J W JaroszewskildquoHPLC-SPE-NMR hyphenation in natural products researchoptimization of analysis of Croton membranaceus extractrdquoMagnetic Resonance in Chemistry vol 43 no 9 pp 771ndash7752005

[14] M T Bayor J S K Ayim G Marston et al ldquoA cytotoxicditerpenoid from Croton membranaceus the major constituentof anticancer herbal formulations used in Ghanardquo NaturalProduct Communications vol 3 no 11 pp 1875ndash1878 2008

[15] J A Sarkodie A A Appiah D A Edoh et al ldquoAntihypergly-caemic and antioxidant effects of Croton membranaceus MullArg (Euphorbiaceae)rdquo International Journal of PharmaceuticalSciences and Research vol 5 no 1 pp 110ndash115 2014

[16] D K Afriyie G A Asare K Bugyei et al ldquoTreatment ofbenign prostatic hyperplasia with Croton membranaceus in anexperimental animal modelrdquo Journal of Ethnopharmacologyvol 157 pp 90ndash98 2014

[17] D KAfriyie G AAsare K Bugyei J Lin J Peng andZHongldquoMitochondria-dependent apoptogenic activity of aqueous rootextract of Croton membranaceus against human BPH-1 cellsrdquoGenetics andMolecularResearch vol 14 no 1 pp 149ndash162 2015

[18] G A Asare A Sittie K Bugyei et al ldquoAcute toxicity studies ofCroton membranaceus root extractrdquo Journal of Ethnopharmacol-ogy vol 134 no 3 pp 938ndash943 2011

[19] D K Afriyie G A Asare K Bugyei I J Asiedu-Gyekye C RTackie and S Adjei ldquoProstate specific targeting of the aqueousroot extract of Croton membranaceus in experimental animalsrdquoAndrologia vol 46 no 7 pp 753ndash760 2014

[20] A A Appiah Phytochemical and biological analysis of Crotonmembranaceus [PhD thesis] Chemistry Department Univer-sity of Ghana 2011

[21] G N Shukla M Nayak and K S Kulkarni ldquoUse of PR-2000a herbal formulation in the medical management of benignprostatic hyperplasiardquo Indian Journal of Clinical Practice vol 13no 2 pp 53ndash56 2002

[22] S Matsumoto T Hanai T Matsui M Oka M Tanaka andH Uemura ldquoEviprostat suppresses urinary oxidative stressin a rabbit model of partial bladder outlet obstruction andin patients with benign prostatic hyperplasiardquo PhytotherapyResearch vol 24 no 2 pp 301ndash303 2010

[23] Y Song N-C Li X-FWang et al ldquoClinical study of Eviprostatfor the treatment of benign prostatic hyperplasiardquo ZhonghuaNan Ke Xue vol 11 no 9 pp 674ndash676 2005

[24] N A Lopatkin A V Sivkov A A Medvedev et al ldquoCombinedextract of Sabal palm and nettle in the treatment of patientswith lower urinary tract symptoms in double blind placebo-controlled trialrdquo Urologiia vol 12 no 2 pp 14ndash19 2006

[25] N Lopatkin A Sivkov S Schlafke P Funk A Medvedev andU Engelmann ldquoEfficacy and safety of a combination of SabalandUrtica extract in lower urinary tract symptomsmdashlong-termfollow-up of a placebo-controlled double-blind multicentertrialrdquo International Urology and Nephrology vol 39 no 4 pp1137ndash1146 2007

[26] F Debruyne G Koch P Boyle et al ldquoComparison of aphytotherapeutic agent (Permixon) with an 120572-blocker (tamsu-losin) in the treatment of benign prostatic hyperplasia a 1-yearrandomized international studyrdquo European Urology vol 41 no5 pp 497ndash507 2002

[27] T Schneider and H Rubben ldquoStinging nettle root extract(Bazoton-uno) in long term treatment of benign prostatic syn-drome (BPS) Results of a randomized double-blind placebocontrolled multicenter study after 12 monthsrdquo Urologe A vol43 no 3 pp 302ndash306 2004

[28] B-X Xue Y-X Shan and G Xiang ldquoClinical evaluation onfengweicao granule in treating benign prostatic hyperplasiardquoZhongguo Zhong Xi Yi Jie He Za Zhi vol 28 no 5 pp 456ndash4582008

[29] A Vidlar J Vostalova J Ulrichova et al ldquoThe effectiveness ofdried cranberries (Vaccinium macrocarpon) in men with lowerurinary tract symptomsrdquo British Journal of Nutrition vol 104no 8 pp 1181ndash1189 2010

[30] P F Engelhardt and C R Riedl ldquoEffects of one-year treatmentwith isoflavone extract from red clover on prostate liver func-tion sexual function and quality of life in men with elevatedPSA levels and negative prostate biopsy findingsrdquo Urology vol71 no 2 pp 185ndash190 2008

[31] M A Borros ldquoClinical significance of measuring prostate-specific antigenrdquo Laboratory Medicine vol 40 no 8 pp 487ndash491 2009

[32] D I Kim JM Song andH C Chung ldquoClinical significance offree-to-total prostate-specific antigen (PSA) ratio in advancedprostate cancer patients with PSA less than 01 ngml afterhormone treatmentrdquo Korean Journal of Urology vol 53 no 3pp 149ndash153 2012

[33] T Jansen and A Daiber ldquoDirect antioxidant properties ofbilirubin and biliverdin Is there a role for biliverdin reductaserdquoFrontiers in Pharmacology vol 3 article 30 2012

[34] K M Wasan D R Brocks S D Lee K Sachs-Barrable and SJ Thornton ldquoImpact of lipoproteins on the biological activity

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 10: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

10 Evidence-Based Complementary and Alternative Medicine

and disposition of hydrophobic drugs implications for drugdiscoveryrdquo Nature Reviews Drug Discovery vol 7 no 1 pp 84ndash99 2008

[35] D K Afriyie G A Asare K Bugyei et al ldquoAnti-atherogenicand anti-ischemic potentials ofCroton membranaceus observedduring sub-chronic toxicity studiesrdquo Pharmacognosy Researchvol 5 no 1 pp 10ndash16 2013

[36] N Talpur B Echard D Bagchi M Bagchi and H G PreussldquoComparison of Saw Palmetto (extract and whole berry) andCernitin on prostate growth in ratsrdquo Molecular and CellularBiochemistry vol 250 no 1-2 pp 21ndash26 2003

[37] Y-S Tsai Y-C Tong J-T Cheng C-H Lee F-S Yang andH-Y Lee ldquoPumpkin seed oil and phytosterol-F can blocktestosteroneprazosin-induced prostate growth in ratsrdquo Urolo-gia Internationalis vol 77 no 3 pp 269ndash274 2006

[38] G F Gonzales V Vasquez D Rodriguez et al ldquoEffect of twodifferent extracts of red maca in male rats with testosterone-induced prostatic hyperplasiardquo Asian Journal of Andrology vol9 no 2 pp 245ndash251 2007

[39] H Azimi A-A Khakshur I Aghdasi M Fallah-Tafti and MAbdollahi ldquoA review of animal and human studies for man-agement of benign prostatic hyperplasia with natural productsperspective of new pharmacological agentsrdquo Inflammation ampAllergymdashDrug Targets vol 11 no 3 pp 207ndash221 2012

[40] M R Safarinejad ldquoUrtica dioica for treatment of benignprostatic hyperplasia a prospective randomized double-blindplacebo-controlled crossover studyrdquo Journal of Herbal Pharma-cotherapy vol 5 no 4 pp 1ndash11 2006

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Page 11: Shrinkage of Prostate and Improved Quality of Life ...downloads.hindawi.com/journals/ecam/2015/365205.pdffunction test (LFT), and the lipid prole were performed. RFT was made up of

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

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