Review ArticlePhellodendri Cortex: A Phytochemical, Pharmacological,and Pharmacokinetic Review

Yue Sun, George Binh Lenon , and AngelaWei Hong Yang

School of Health and Biomedical Sciences, RMIT University, Victoria, Australia

Correspondence should be addressed to George Binh Lenon; george.lenon@rmit.edu.au

Received 18 November 2018; Accepted 5 February 2019; Published 26 March 2019

Guest Editor: Jesus R. R. Amado

Copyright © 2019 Yue Sun et al. This is an open access article distributed under the Creative Commons Attribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background. Phellodendri Cortex (PC) or Huang Bai. According to the scientific database of China Plant Species and Chinesepharmacopeia 2015 edition, PC has two main species which are Phellodendron amurense Rupr (PAR) or “Guan Huang bai”in Chinese and Phellodendron chinense Schneid (PCS) or “Chuan Huang bai” in Chinese. The crude drugs of PAR and PCSare also called Phellodendri amurensis cortex (PAC) and Phellodendri chinense cortex (PCC), respectively. The medicinal partof the plant is the dried trunk bark. PC has comprehensive therapeutic effects which include anti-inflammatory, antimicrobial,anticancer, hypotensive, antiarrhythmic, antioxidant, and antipyretic agents. The exact ingredients in PC and its species are notfully summarised. Aim of the Study.This study was designed to review and evaluate the pharmacological actions of compounds andto explore the pharmacokinetic knowledge of PC and its species and to also identify the chemical compound(s) with a potentialtherapeutic effect on atopic dermatitis. Methods. “Huang Bai” and its English, botanical, and pharmaceutical names were used askeywords to perform database search in Encyclopaedia of traditional Chinese Medicines, PubMed, EMBASE, MEDLINE, ScienceDirect, Scopus, Web of Science, and China Network Knowledge Infrastructure.The data selection criteria included all the studiesthat were related to the phytochemical, pharmacological, and pharmacokinetic perspectives of PC and its species or their activeconstituents. More importantly, the voucher number has been provided to ensure the genuine bark of PC used as the medicinalpart in the studies. Results. 140 compounds were summarized from PC and its species: specifically, 18 compounds from PCC,44 compounds from PCS, 34 compounds from PAC, and 84 compounds from PAR. Obacunone and obaculactone are probablyresponsible for antiatopic dermatitis effect. PC and its species possess a broad spectrum of pharmacological actions including anti-inflammatory effect, antibacterial effect, antiviral effect, antitumor effect, antigout effect, antiulcer effect, neuroprotective effect, andantiatopic dermatitis effect. PC could widely distribute in plasma, liver, spleen, kidney, and brain. Berberine may be responsiblefor the toxic effect on the susceptible users with hemolytic disease or in the peripartum and neonatal period. Conclusions. Thecompounds of the crude bark of PC and its subspecies have showcased a wide range of pharmacological effects. Pharmacologicalefficacies of PC are supported by its diverse class of alkaloid, limonoid, phenolic acid, quinic acid, lignan, and flavonoid. Obacunoneand obaculactone could be the bioactive compounds for atopic dermatitis management. PC and its subspecies are generally safe touse but extra care is required for certain conditions and group of people.

1. Introduction

Phellodendri Cortex (PC) is also known as “Huang bai” inChinese and “Obaku” in Japanese. PC is a plant grown inChina, Korea, Japan, Vietnam, and Far East of Russia. Theearliest record of this plant was on “Shennong’s Classic ofMateria Medica” [1]. According to the scientific database ofChina Plant Species and Chinese pharmacopeia 2015 edi-tion, PC has two main species which are Phellodendronamurense Rupr (PAR) or “Guan Huang bai” in Chinese and

Phellodendron chinense Schneid (PCS) or “Chuan Huangbai” in Chinese. The crude drugs of PAR and PCS arecalled Phellodendri amurensis cortex (PAC) and Phelloden-dri chinense cortex (PCC), respectively. PAR and PCS arenaturally grown in the Northeast and Southwest part ofChina, respectively [2]. According to the latest informationfrom “information system of Chinese rare and endangeredplants,” PAR is categorized as one of the second degrees ofendangered plants. PAR and PCS could be interchangeablyused in clinical application because both species contain

HindawiEvidence-Based Complementary and Alternative MedicineVolume 2019, Article ID 7621929, 45 pageshttps://doi.org/10.1155/2019/7621929

2 Evidence-Based Complementary and Alternative Medicine

similar chemical constituents [3]. According to the scientificdatabase of China Plant Species and Chinese pharmacopeia2015 edition, PC is categorized in the family of PhellodendronRupr. The medicinal part of the plant is the dried trunk bark.PC had been viewed as one of the 50 fundamental herbsin Chinese herbalism. Traditionally, its medicinal part couldexert therapeutic effects in various diseases such as meningi-tis, cirrhosis, dysentery, pneumonia, tuberculosis, etc. [4, 5].Nowadays, PC has comprehensive therapeutic effects whichinclude immune modulation, anti-inflammatory, antimicro-bial, antibacterial, anticancer, hypotensive, antiarrhythmic,antioxidant, antigastric ulcer, and antipyretic agents, etc. [5].According to the Clinical Chinese Materia Medica, 2006edition, PC has a bitter flavor and cold nature and canenter the meridian of kidney, bladder, and large intestine.PC could clear heat, dry dampness, drain fire, eliminatesteam, resolve toxin, and treat sores [6]. PC and its speciescontain various chemical derivatives. One of the importantones is alkaloids which contain berberine and jatrorrhizine.Both compounds were proven to be effective against sometype of tumours, infections, neurological diseases [7]. Tofurther acquire the knowledge on PC, a systematic reviewof its phytochemical, pharmacological, and pharmacokineticproperties is required. The aim of this study is to review andevaluate the pharmacological actions of compounds as wellas to explore the pharmacokinetic knowledge of the PC andits species. The chemical compounds that exert therapeuticeffect for atopic dermatitis are also desired.

2. Methods

Data were searched from the following databases untilMay 2018: Encyclopaedia of Traditional Chinese Medicines;PubMed; EMBASE; MEDLINE; ScienceDirect; SCOPUS;Web of Science; China Network Knowledge Infrastructure.The keywords used for the literature search included: HuangBai and its English, botanical, and pharmaceutical names.The selection criteria included process controls of the herbalsubstances, reporting reference standards such as authenti-cation of reference materials and profile chromatograms, andanalytical procedures and validation data. Papers in Englishor Chinese language are included for this review. Scientificrigidity was determined by the chemical markers of herbsthrough the use of strict parameters in testing, quantitative,and qualitativemeasures of the bioactive components, such ashigh-performance liquid chromatography, fingerprint spec-trum, correlations differentiation, and stability evaluation,reference standards, and toxicological assessments. Plantvoucher specimens are a guarantee for traceability of theplant material and data verification for other researchers orcommercial purposes [60]. The chemical formulas of thecompounds of PC and its species were acquired from selectedstudies. Chemical structures and molecular weights wereextracted from ChemDraw professional 170.

3. Results

A total of 125 papers were identified through the litera-ture search. Fifty-two papers were excluded based on the

reasons for nonpharmacodynamic, nonphytochemistry, andnonpharmacological studies. 73 studies fitted the selectioncriteria. Among these articles, 32 studies are about pharmaco-dynamics, 38 studies are about phytochemistry, and 3 studiesare about pharmacokinetics (Figure 1).

4. Bioactive Compounds

The crude barks of PC and its species contain alkaloids,isoquinoline alkaloid, limonoids, phenolic acid, quinic acid,lignans, and flavonoid, and so on. A summary of the bioactivecompounds of the PC and its species reported in the includedstudies is presented in Table 1. Molecular formula, molecularweight, and chemical structure of the major constitutedalkaloids of PC, including berberine, palmatine, and jatror-rhizine, are listed in Tables 2, 3, 4, and 5. They could exert abroad spectrumof pharmacological influence which containsantimicrobial, anti-inflammation, antitumor, antidepressant,and antiulcer effects [47]. Limonoids including limonin andobakunone play an important role in the anti-inflammatoryeffects of PC [11]. Phenolic acid or phenol carboxylic acidsbelong to aromatic acid compound substances which arecharacterized by a phenolic ring and an organic carboxylicacid function [61]. According to the description on Buchlerquinine plant in Braunschweig, Germany, quinic acid is anatural sugary compound which can be found in multipleplants such as well-known coffee beans and tobacco leaves.Based on the description on PubChem, lignans affiliate aclass of dibenzylbutane derivatives which exists in plantsand in body fluids such as bile, serum, urine, etc. Thesecompounds have anticancer potential. Quercetin belongs toflavonoids which can reduce coronary heart disease accord-ing to PubChem data. Two species of PC, PCS and PAR,can be differentiated based on the contents of the chemicalcompounds. Specifically, the 2005 edition of Chinese Medic-inal encyclopedia described the PCS’s minimal content ofberberine hydrochloride and phellodendron hydrochlorideto be 3.0% and 0.34%, respectively; the PAR’sminimal contentof berberine hydrochloride and palmatine hydrochloride is0.60% and 0.30%, respectively [62].

5. Pharmacology

5.1. Anti-Inflammatory Effects. The PAR extract could effi-ciently adjust lipopolysaccharide (LPS)-induced release ofnitric oxide (NO) and inducible nitric oxide sythase (iNOS)production in microglia of both BV2 cells and mice. Besides,PAR extract could also attenuate the LPS-stimulated releaseof tumor necrosis factor-𝛼 (TNF-𝛼) and interleukin 1𝛽 (IL-1𝛽) from microglia. More importantly, the latter mechanismis more significant than the previous one in terms of IL-1𝛽 release. The inhibition of NO suggested that the extractof PAR probably could affect NO-induced neuronal celldeath [28]. Another study had also vindicated the anti-inflammatory effect of PC extract on ear swelling modelof mice. Magnoflorine and phellodenrine belong to alka-loids isolated from PC that are the effective compoundsagainst oxazolone-induced contact-delayed type hypersensi-tivity (DTH) reaction induced by picryl chloride. Another

Evidence-Based Complementary and Alternative Medicine 3

Iden

tifica

tion

Scre

enin

gEl

igib

ility

Inclu

ded

125 articles

73 included

73 included

Pharmacodynamics: 32 Photochemistry: 38 Pharmacokinetic: 3

52 excluded due to irrelevance to pharmacodynamics, photochemistry, and pharmacokinetic

Figure 1: PC study selection flowchart.

mechanism in this study is that PC could reduce myeloper-oxidase (MPO) activity to its utmost by restraining leukocytemobility and/or a secretory activity by phellodendron. Incontrast, PC extract exerts no effect on phospholipase A2(PLA2) activity and less effect in arachidonic acid (AA)

induced swelling [29]. PC showcased the inhibitory effecton the build-up of NO in LPS-stimulated macrophage Raw264.7 cells and inhibited iNOS expression. In contrast, PC hasno effect on cyclooxygenase-2 (COX-2) expression in LPS-induced RAW 264.7 cells [30]. PCC and PAC could not onlyshrink the size of edema, but also reduce the activity of MPOand the content of reactive oxygen species (ROS) causedby 12-O-tetradecanoyl-phorbol-13-acetate (TPA). They canalso restrain the levels of TNF-𝛼, Il-1𝛽, IL-6, and COX-2 in mice treated by TPA. Remarkably, there are a num-ber of chemical compounds in these two species of PCincluding berberine, palmatine, and phellodendrine. Andthey are viewed as the anti-inflammatory active candidates.In addition, they may jointly take effect in this regard [3].The nonalkaloid PAR extract suppressed NO production;besides, limonin and obakunone significantly downregulatedNO production and iNOS gene expression via an nuclearfactor-𝜅B (NF-𝜅B)-mediated pathway [11]. PC could reversethe airway inflammation by reducing the infiltration ofinflammatory cells and releasing of inflammatory media-tors into the affected lung and airways. This could vindi-cate its applications on the infectious pulmonary diseases[31].

5.2. Antimicrobic Effects. For the antibacterial effect, thestudy showed both aqueous and ethanol extracts of PARexerted an intermediate antimicrobial effect. Besides, PARextracts had a slightly better effect on gram-positive bacteriathan gram-negative one because of different sensitivity. Themost sensitive bacteria is Streptococcus pyogenes [33]. Forthe bacteria in the oral cavity, PC could have a stronginhibitory effect on Porphyromonas gingivalis; moderateinhibitory effect on Streptococcus mutans; partial effect onStreptococcus sanguis; no effect on Streptococcus mitis [34].Propionibacterium acnes which are the culprit for acneis active to PC which is one of the crude herbs in theclinical trial and the second best herb in terms of antiacneactivity in this study [39]; Mycoplasma hominis which causesinfections on humans genital tracts and respiratory tractsis susceptive to PC, and the susceptibility rate is 93% [35].Salmonellosis which is responsible for food poisoning isvulnerable to PC extract because it can lower the IgG levelsand induce TNF-𝛼 expression in RAW264.7 cells [36]. Incase of PAR, berberine could restrain the bacterial adhesionof Staphylococcus aureus and intracellular invasion intohuman gingival fibroblasts [37]. Moreover, berberine couldattenuate the aminoglycoside resistance of P. aeruginosa, A.xylosoxidans, and B. cepacia in the MexXY-dependent man-ner. It also inhibits MexXY- or MexVW-mediated resistanceof P. aeruginosa mutants, synergistically restrains MexXY-mediated gentamicin resistance in P. aeruginosamutants, andenhances the synergistic effect of piperacillin and amikacin in

4 Evidence-Based Complementary and Alternative Medicine

Table1:Summaryof

chem

icalconstituentsisolatedfro

mPC

andits

different

species(140compo

unds).

Com

poun

dderiv

atives

Chem

icalcompo

unds

Metho

dsRe

ferences

Orig

inalspecies

Alkaloid

Berberine

(i)UPL

C-ES

I-Q-TOF-MS

(i)[8]

(i)PA

C(ii)H

PLC-

DAD-ESI-M

S2(ii)[9]

(ii)P

CSandPA

R(iii)UPL

C-Q/TOF-HDMS

(iii)[10]

(iii)PA

C(iv

)HPL

C-TL

C-NMR-EI-M

S(iv

)[11]

(iv)P

AR

(v)H

PLC-

DAD-M

S(v)[12]

(v)P

AR

(vi)N/A

(vi)[13]

(vi)PA

CandPC

S8,13-dioxo-14-bu

toxycanadine

CC

[14]

PCS

Berberrubine

UPL

C-ES

I-Q-TOF-MS

[8]

PAC

Berberastin

eUPL

C-Q/TOF-HDMS

[10]

PAC

Bis-[4-(dimethylamino)ph

enyl]m

ethano

neHPL

C-ES

I-MS/MS

[15]

PAR

Brucine

CE[16]

PCS

Δ7-dehydrosoph

oram

ine

N/A

[17]

PAC

Dihydrocyclob

uxine-D

HPL

C-ES

I-MS/MS

[15]

PAR

3,4-dihydro-1-[(4-hydroxyph

enyl)m

ethyl]-7-metho

xy-2-

methyl-8

-isoq

uino

linol

HPL

C-ES

I-MS/MS

[15]

PAR

3,4-dihydro-1-[(4-hydroxyph

enyl)m

ethyl]-7-metho

xy-2-

methyl-6

-isoq

uino

linol

HPL

C-ES

I-MS/MS

[15]

PAR

7,8-dihydroxyrutaecarpine

HPL

C-ES

I-MS/MS

[15]

PAR

4-dimethylamino-4-is

opropylbenzene

HPL

C-ES

I-MS/MS

[15]

PAR

Evod

iamine

HPL

C-ES

I-MS/MS

[15]

PAR

Palm

atine

(i)UPL

C-ES

I-Q-TOF-MS

(i)[8]

(i)PA

C(ii)H

PLC-

DAD-ESI-M

S2(ii)[9]

(ii)P

CSandPA

R(iii)UPL

C-Q/TOF-HDMS

(iii)[10]

(iii)PC

C(iv

)HPL

C-DAD-M

S(iv

)[12]

(iv)P

AR

(v)N

/A(v)[18]

(v)P

CSTetrahydropalm

atine

UPL

C-ES

I-Q-TOF-MS

[8]

PAC

Tetrahydroberberine

HPL

C-ES

I-MS/MS

[15]

PAR

Phellodend

rine

(i)UPL

C-ES

I-Q-TOF-MS

(i)[8]

(i)PA

C(ii)H

PLC-

DAD-ESI-M

S2(ii)[9]

(ii)P

CSandPA

R(iii)UPL

C-Q/TOF-HDMS

(iii)[10]

(iii)PA

C(iv

)HPL

C-DAD-M

S(iv

)[12]

(iv)P

AR

(v)N

/A(v)[18]

(v)P

ACandPC

S

Evidence-Based Complementary and Alternative Medicine 5Ta

ble1:Con

tinued.

Com

poun

dderiv

atives

Chem

icalcompo

unds

Metho

dsRe

ferences

Orig

inalspecies

Magno

curarin

e(i)

HPL

C-ES

I-MS/MS

(i)[15]

(i)PA

R

Magno

florin

e

(i)HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

CC

(iii)HPL

C-DAD-M

S(iii)[12]

(iii)PA

R(iv

)N/A

(iv)[19]

(iv)P

CS

Jatro

rrhizine

orNeprotin

,2,9,10-Trim

etho

xy-5,6-

dihydroisoqu

inolino[2,1-b

]isoq

uino

lin-7-iu

m-3-ol

(i)UPL

C-ES

I-Q-TOF-MS

(i)[8]

(i)PA

C(ii)H

PLC-

DAD-ESI-M

S2(ii)[9]

(ii)P

CSandPA

R(iii)HPL

C-DAD-M

S(iii)[12]

(iii)PA

R(iv

)N/A

(iv)[19]

(iv)P

AC13-m

etho

xyjatro

rrhizine

HPL

C-ES

I-MS/MS

[15]

PAR

�-Fagarine

CC

[20]

PAR

Canthin-6-one

CC

[20]

PAR

4-metho

xy-N

-methyl-2

-quino

lone

CC

[20]

PAR

Oxypalm

atine

CC

[20]

PAR

Candicine

HPL

C-DAD-ESI-M

S2[9]

PAR

Lotusin

e(i)

HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

ACN-m

ethylhigenam

ine-7-O-glucopyrano

side

HPL

C-ES

I-MS/MS

[15]

PAR

N-m

ethylhigenam

ine-7-O-𝛽-D

-glucopyrano

side

HPL

C-DAD-ESI-M

S2[9]

PAR

(−)-Oblon

gine

(i)HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

CC

Isom

er-of-b

erberin

eHPL

C-DAD-ESI-M

S2[9]

PAR

Isom

er-of-m

agno

florin

eHPL

C-DAD-ESI-M

S2[9]

PCSandPA

RIsom

er-of-p

almatine

HPL

C-DAD-ESI-M

S2[9]

PAR

Tetrahydroretic

uline

HPL

C-DAD-ESI-M

S2[9]

PAR

Tetrahydrojatro

rrhizine

HPL

C-DAD-ESI-M

S2[9]

PCSandPA

R

Menisp

erine

(i)HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

CC

(iii)N/A

(iii)[19

](iii)PA

C(+)N

-methylcorydine

HPL

C-DAD-ESI-M

S2[9]

PAR

N-m

ethylTetrahydrop

almatine

HPL

C-ES

I-MS/MS

[15]

PAR

N-m

ethylflindersine

HPL

C-ES

I-MS/MS

[15]

PAR

Litcub

ine

HPL

C-DAD-ESI-M

S2[9]

PAR

Hydroxyl-p

almatine

HPL

C-DAD-ESI-M

S2[9]

PAR

11-hydroxylpalm

atine

HPL

C-ES

I-MS/MS

[15]

PAR

13-hydroxypalm

atine

HPL

C-ES

I-MS/MS

[15]

PAR

7-hydroxy-8-metho

xydedihydrorutaecarpine

HPL

C-ES

I-MS/MS

[15]

PAR

Tetrahydropalm

atine

HPL

C-DAD-ESI-M

S2[9]

PAR

Xantho

planine

HPL

C-DAD-ESI-M

S2[9]

PAR

N-m

ethylpho

ebine

HPL

C-DAD-ESI-M

S2[9]

PAR

Colum

bamine

HPL

C-DAD-ESI-M

S2[9]

PCSandPA

RDihydroxyl-jatrorrhizine

HPL

C-DAD-ESI-M

S2[9]

PAR

Epiberberin

eHPL

C-DAD-ESI-M

S2[9]

PAR

6 Evidence-Based Complementary and Alternative Medicine

Table1:Con

tinued.

Com

poun

dderiv

atives

Chem

icalcompo

unds

Metho

dsRe

ferences

Orig

inalspecies

(6aS)-1,2

,10,11-te

tram

etho

xy-6,6-dim

ethyl-5

,6,6a,7

-tetrahydro-

4H-dibenzo[de,g]

quinolinium

UPL

C-Q/TOF-HDMS

[10]

PCC

Dasycarpamin

UPL

C-Q/TOF-HDMS

[10]

PCC

Pteleine

HPL

C-UV

[21]

PAR

(-)-(R)-platydesmin

HPL

C-UV

[21]

PAR

Noroxyhydrastinine

HPL

C-UV

[21]

PAR

Chilenine

HPL

C-UV

[21]

PAR

Rutecarpine

HPL

C-ES

I-MS/MS

[15]

PAR

Skim

mianine

HPL

C-ES

I-MS/MS

[15]

PAR

Tembetarin

eHPL

C-ES

I-MS/MS

[15]

PAR

Tetram

ethyl-O

-scutellarin

UPL

C-Q/TOF-HDMS

[10]

PCC

5,8,13,13

a-Tetrahydro-2,9,10,11-te

trahydroxy-3-m

etho

xy-7-

methyl-6

H-dibenzo[a,g]

quinolizinium

HPL

C-ES

I-MS/MS

[15]

PAR

�-hydroxybu

teno

lided

erivatives

IIUPL

C-Q/TOF-HDMS

[10]

PCC

Evidence-Based Complementary and Alternative Medicine 7

Table1:Con

tinued.

Com

poun

dderiv

atives

Chem

icalcompo

unds

Metho

dsRe

ferences

Orig

inalspecies

Isoq

uino

linea

lkaloid

Arm

epavine

UPL

C-ES

I-Q-TOF-MS

[8]

PAC

Dem

ethyleneberberine

UPL

C-ES

I-Q-TOF-MS

[8]

PAC

8-oxob

erberin

eHPL

C-ES

I-MS/MS

[15]

PAR

8-oxoepiberberine

HPL

C-ES

I-MS/MS

[15]

PAR

8-oxop

almatine

HPL

C-ES

I-MS/MS

[15]

PAR

Oxyberberine

HPL

C[20]

PAR

Oxypalm

atine

HPL

C[20]

PAR

Limon

oid

KihadaninB

N/A

[19]

PAC

Nilo

ticin

N/A

[18]

PAC

Nilo

ticin

acetate

N/A

[18]

PCS

Obaculacton

eorlim

onin

(i)UPL

C-ES

I-Q-TOF-MS

(i)[8]

(i)PA

C(ii)C

C(ii)[20]

(ii)P

AR

(iii)UPL

C-Q/TOF-HDMS

(iii)[10]

(iii)PC

C(iv

)HPL

C-TL

C-NMR-

EI-M

S(iv

)[11]

(iv)P

AC(v)N

/A(v)[18]

(v)P

ACDerivativeo

fobaculacton

eUPL

C-Q/TOF-HDMS

[10]

PCC

Obacuno

neor

Obacuno

icacid

(i)CC

(i)[20]

(i)PA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

CC

(iii)HPL

C-TL

C-NMR-

EI-M

S(iii)[11]

(iii)PA

C

(iv)H

PLC-

DAD-ESI-M

S2(iv

)[9]

(iv)P

AR

(v)N

/A(v)[18]

(v)P

AC12𝛼-hydroxylim

onin

CC

[20]

PAR

PiscidinolA

N/A

[18]

(i)PC

S

Rutaevin

(i)HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

CC

Con

iferin

HPL

C-DAD-ESI-M

S2[9]

PAR

Vanillo

losid

eHPL

C-DAD-ESI-M

S2[9]

PAR

N-m

ethyltetrahydrocolumbamine

UPL

C-Q/TOF-HDMS

[10]

PCC

N-acylamines

Herculin

N/A

[19]

PAC

8 Evidence-Based Complementary and Alternative MedicineTa

ble1:Con

tinued.

Com

poun

dderiv

atives

Chem

icalcompo

unds

Metho

dsRe

ferences

Orig

inalspecies

Phenolicacid

Ferulic

acid

(i)HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)H

PLC-TL

C-NMR-

EI-M

S(ii)[11]

(ii)P

ACMethylferulate

CC

[4]

PCS

Protocatechu

icacid

CC

[4]

PCS

Quinica

cid

Quinica

cid

UPL

C-Q/TOF-HDMS

[10]

PAC

Neo-chlorogenicacid

HPL

C-DAD-ESI-M

S2[9]

PCSandPA

R

3-O-fe

ruloylqu

inicacid

(i)HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

AC3-O-fe

ruloylqu

inicacid

glucoside

UPL

C-Q/TOF-HDMS

[10]

PCC

4-O-fe

ruloylqu

inicacid

HPL

C[22]

PCS

5-O-fe

ruloylqu

inicacid

HPL

C[22]

PCS

Chlorogenica

cid

(i)HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

AC(iii)HPL

C(iii)[23]

(iii)PA

R(iv

)HPL

C-DAD-M

S(iv

)[12]

(iv)P

AR

Methyl3-O

-feruloylqu

inate

HPL

C-DAD-ESI-M

S2[9]

PAR

Methyl5-O

-feruloylqu

inate

NMR

[24]

PAR

3-Feruoyl-4

-caffeoylqu

inicacid

HPL

C-DAD-ESI-M

S2[9]

PAR

Sanlengacid

NMR

[25]

PAC

Hydroxycinn

amicacid

CaffeicA

cidMethylE

ster

HPL

C[22]

PCS

Phytosterol

𝛽-Sito

sterol

N/A

[18]

PAC

Lign

an(+/-)-lyon

iresin

olHPL

C-DAD-ESI-M

S2[9]

PAR

(+/-)-5,5�耠-dim

etho

xylaric

iresin

ol-4-O

-glucosid

e(i)

HPL

C-DAD-ESI-M

S2(i)

[9]

(i)PC

SandPA

R(ii)U

PLC-

Q/TOF-HDMS

(ii)[10]

(ii)P

CC

Syrin

garesin

oldi-O

-𝛽-D

-glucopyrano

side

HPL

C-DAD-ESI-M

S2[9]

PCSandPA

R(-)-Syrin

garesin

olCC

[4]

PCS

Flavon

oid

Amurensin

N/A

[13]

PAC

Quercetin

HPL

C-TL

C-NMR-

EI-M

S[11]

PAC

Phellamurin

N/A

[18]

PAC

Phellatin

N/A

[18]

PAC

Phellavin

N/A

[18]

PAC

Phellodend

rosid

eN/A

[18]

PAC

𝛽-anh

ydrono

ricaritin

UV

[26]

PAR

Icariside-1

UV

[26]

PAR

Phellamuretin

UV

[26]

PAR

Phellosid

eUV

[26]

PAR

Dihydroph

ellosid

eUV

[26]

PAR

Isovalericacid

UV

[26]

PAR

Kaem

pferol

UV

[26]

PAR

D-glucose

UV

[26]

PAR

Rutaceae

Noricariside

N/A

[18]

PAC

Stigmastane

7-Dehydrostigm

asterol

N/A

[17]

PAC

Cou

marin

3-acetyl-3,4-dihydro-5,6-dim

etho

xy-1H-2-benzopyran-1-o

neCC

[27]

PCS

Evidence-Based Complementary and Alternative Medicine 9

Table1:Con

tinued.

Com

poun

dderiv

atives

Chem

icalcompo

unds

Metho

dsRe

ferences

Orig

inalspecies

Mon

osaccharide

Syrin

gin

NMR

[25]

PAC

Daucoste

rol

NMR

[25]

PAC

Paraben

N-propylparaben

HPL

C[5]

PCPh

enoliclacton

ePh

ellolacton

eCC

[4]

PCS

Ferulate

N-butylFerulate

CC

[4]

PCS

Amurenlacton

eACC

[4]

PCS

Amurenam

ideA

NMR

[25]

PAC

Hydroxybenzaldehyde

4-hydroxybenzaldehyde

CC

[4]

PCS

Phenolicaldehyde

Vanillin

CC

[4]

PCS

Glycosid

eSinapylaldehyde-4-O-beta-D-glucopyrano

side

NMR

[24]

PAR

3,4,5-Trim

etoxypheno

lO-𝛽-D

-glucopyrano

side

HPL

C[22]

PCS

2-metho

xy-4-(2-prop

enyl)phenyl-b

eta-D-glucopyrano

side

HPL

C[22]

PCS

2-(p-hydroxyph

enyl)-ethano

l-1-O

-𝛽-D

-apiofuranosyl

(1–6

)-O-𝛽-D

-glucopyrano

side

HPL

C-DAD-ESI-M

S2[9]

PCSandPA

R

2-(p-hydroxyph

enyl)-ethano

l-1-O

-𝛽-D

-glucosid

eUPL

C-Q/TOF-HDMS

[10]

PCC

3,5-dihydroxybenzoicacid-O

-xylop

yranosyl-glucopyrano

side

HPL

C-DAD-ESI-M

S2[9]

PCSandPA

RPh

enolicglycoside

Tachiosid

eHPL

C[22]

PCS

Glucosid

eSalid

rosid

eHPL

C[22]

PCS

4-hydroxybenzylalcoh

olHPL

C[22]

PCS

Phenol

Methylsyringate

HPL

C[22]

PCS

Dehydrovomifo

liol

(6S)-dehydrovomifo

liol

HPL

C[22]

PCS

(6R,7aR)-epilolio

lide

HPL

C[22]

PCS

PAC:

phellodend

riam

urensis

cortex

PCS:ph

ellodend

ronchinense

schn

eid

PAR:

phellodend

ronam

urense

rupr.

PCC:

phellodend

riCh

inensis

cortex

UPL

C-ES

I-Q-TOF-MS:ultra-perfo

rmance

liquidchromatograph

ycoup

ledwith

electro

sprayionizatio

n/qu

adrupo

le-time-of-flight

massspectrometry

CC:colum

nchromatograph

yCE

:capillaryelectro

phoresis

HPL

C/MSD

:high-perfo

rmance

liquidchromatograph

ycoup

ledwith

massspectrometric

detection

UPL

C–Qthe-TOF-MS:ultra-perfo

rmance

liquidchromatograph

ywith

quadrupo

leTO

F-MS

HPL

C–ES

I-MS2:high-perfo

rmance

liquidchromatograph

ywith

electro

sprayionizatio

nmassspectrometry

coup

ledwith

photod

iode

arraydetection

UPL

C-Q/TOF-HDMS:ultra-perfo

rmance

liquidchromatograph

y-qu

adrupo

le/time-of-flight

high-definitio

nmassspectrometry

UV:

UVdetection

EI-M

S:Electro

nionizatio

nmassspectrometry

NMR:

Nuclear

magnetic

resonance

TLC:

Thin-la

yerc

hrom

atograph

yHPL

C-DAD-M

S:high-perform

ance

liquidchromatograph

ycoup

ledwith

diod

earray

detectionandmassspectrometry

10 Evidence-Based Complementary and Alternative MedicineTa

ble2:Molecular

form

ula,molecular

weight

andchem

icalstr

uctureso

fcom

poun

dsderiv

edfro

mPC

Cspecies(18

compo

unds).

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Alkaloid

Palm

atine

C 21H22NO4

+352.41g/mol

ON

+

O

O

O

Palm

atin

e

Magno

florin

eC 20H24NO4

+342.41

g/mol

N+

HO

HOO O

Mag

noflo

rine

(−)-Oblon

gine

C 19H24NO3

+314.40

g/mol

N+

OH

O

OH

Obl

ongi

ne

Menisp

erine

C 21H26NO4

+356.44

g/mol

N+

H

H3C

O

MeO H

O

MeO

H

CH3

CH3

11-h

ydro

xy-1

,2,1

0-tr

imet

hoxy

-6,6

-dim

ethy

l-5,6

,6a,7

-tetr

ahyd

ro-4H-

dibe

nzo[de,g]

quin

olin

-6-iu

m

(6aS)-1,2

,10,11-te

tram

etho

xy-6,6-dim

ethyl-5

,6,6a,7

-tetrahydro-4H-dibenzo[de,g]

quinolinium

C 22H28NO4

370.47

g/mol

O

O

N+

O

O

(6aS

)-1,

2,10

,11-

tetr

amet

hoxy

-6,6

-dim

ethy

l-5,6

,6a,7

-tetr

ahyd

ro-4

H-d

iben

zo[d

e, g]

qu

inol

iniu

m

Dasycarpamin

C 17H21NO4

303.36

g/mol

N HO

O

O

O

4,7,

8-tr

imet

hoxy

-3-[

(E)-

3-m

ethy

lbut

-1-e

nyl]-

1H-q

uino

lin-2

-one

Tetram

ethyl-O

-scutellarin

C 19H18O6

342.35

g/mol

OO

O

OO

O

5,6,

7-tr

imet

hoxy

-2-(

4-m

etho

xyph

enyl

)chr

omen

-4-o

ne

Evidence-Based Complementary and Alternative Medicine 11

Table2:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

�-hydroxybu

teno

lided

erivatives

IIN/A

Limon

oid

Nilo

ticin

acetate

C 32H50O4

498.75

g/mol

O

H

H

O

O

O

Nilo

ticin

acet

ate

Obaculacton

eorlim

onin

C 26H30O8

470.52

g/mol

O

OO

O

O

O

O

O

H

H

limon

in

Derivativeo

fobaculacton

eN/A

Obacuno

neor

Obacuno

icacid

C 26H30O7

454.519g

/mol

O

O

O

O

O

H

HO

O

Oba

cuno

ne

PiscidinolA

C 30H50O4

474.73

g/mol

OH O

H

HO

O

Pisc

idin

ol A

Rutaevin

C 26H30O9

486.52

g/mol

O

OH

O

HO

OH

O

O

O

H

O

Ruta

evin

N–m

ethyltetrahydrocolumbamine

C 21H26NO4

+356.44

g/mol

HO

O

N+

CH3

O

O

2-hy

drox

y-3,

9,10

-trim

etho

xy-7

-met

hyl-5

,6,7

,8,1

3,13

a-he

xahy

droi

soqu

inol

ino[

3,2-a]

isoqu

inol

in-7

-ium

12 Evidence-Based Complementary and Alternative Medicine

Table2:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Phenolicacid

2-(p-hydroxyph

enyl)-ethano

l-1-O

-𝛽-D

-glucosid

eC 9

H12O

136.19

g/mol

OH

OA

PI(1

6)

glu

2-(p

-hyd

roxy

phen

yl)-

etha

nol-1

-O-b

eta-

D-a

piof

uran

osyl

(1-6

)-O

-bet

a-D

-glu

copy

rano

side

Quinica

cid

3-O-fe

ruloylqu

inicacid

glucoside

C 22H28O15

532.45

g/mol

3-O

-feru

loyl

quin

ic ac

id g

luco

side

OH

OH

OH

abs

abs

abs

abs

OH

HO

HO

HO

HO

HO

O

O

O

O

O

O

Lign

an(+/-)-5,5�耠-dim

etho

xylaric

iresin

ol-4-O

-glucosid

eC 28H38O13

582.6g/mol

O

HO

H2C

H3C

O

OCH

3

OCH

3

OH

OCH

3

OCI

G

(+/-

)-5,

5'-di

met

hoxy

laric

iresin

ol-4

-O-g

luco

side

Evidence-Based Complementary and Alternative Medicine 13

Table3:Molecular

form

ula,molecular

weight

andchem

icalstr

uctureso

fcom

poun

dsderiv

edfro

mPC

Sspecies(44

compo

unds).

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Alkaloid

Berberine

C 20H18NO4

+336.37

g/mol

O

O

N+

O

O

Berb

erin

e

8,13-dioxo-14-bu

toxycanadine

C 24H25NO7

439.4

6g/m

olO

N

OCH

3

OCH

3

H3C

H2C

H2C

H2C

O

O

O

13a-

buto

xy-9

,10-

dim

etho

xy-5

,13a

-dih

ydro

-6H

-[1,

3]di

oxol

o[4,

5-g]

isoqu

inol

ino[

3,2-a]

isoqu

inol

ine-

8,13

-di

one

Brucine

C 23H26N2O4

394.47

g/mol

O ON O

O

H

H

H

HN

Bruc

ine

Palm

atine

C 21H22NO4

+352.41g/mol

ON

+

O

O

O

Palm

atin

e

Phellodend

rine

C 20H24NO4

+342.41

g/mol

N+

H

OHO

OH

O

Phel

lode

ndrin

e

Magno

florin

eC 20H24NO4

+342.41

g/mol

N+

HO

HOO O

Mag

noflo

rine

Jatro

rrhizine

orNeprotin

,2,9,10-Trim

etho

xy-5,6-

dihydroisoqu

inolino[2,1-b

]isoq

uino

lin-7-iu

m-3-ol

C 20H19NO4

337.3

8g/m

olN

+

O- O

O O

Jatro

rrhi

zine

Lotusin

eC 19H24NO3

+314.40

g/mol

N+

HO

H3C

O

H

OH

CH3

CH3

(S)-

6-hy

drox

y-1-

(4-h

ydro

xybe

nzyl

)-7-

met

hoxy

-2,2

-dim

ethy

l-1,2

,3,4

-te

trah

ydro

isoqu

inol

in-2

-ium

(−)-Oblon

gine

C 19H24NO3

+314.40

g/mol

N+

H

H3C

O

OH

OH

CH3

CH3

(S)-

8-hy

drox

y-1-

(4-h

ydro

xybe

nzyl

)-7-

met

hoxy

-2,2

-dim

ethy

l-1,2

,3,4

-tetr

ahyd

roiso

quin

olin

-2-

ium

14 Evidence-Based Complementary and Alternative MedicineTa

ble3:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Isom

er-of-m

agno

florin

eN/A

Tetrahydrojatro

rrhizine

C 20H23NO4

341.4

1g/m

olN

H3C

O

H3C

O

OH OCH

3

2,3,

10-tr

imet

hoxy

-5,8

,13,

13a-

tetr

ahyd

ro-6H

-isoq

uino

lino[

3,2-a]

isoqu

inol

in-9

-ol

Menisp

erine

C 21H26NO4

+356.44

g/mol

N+

H

H3C

O

MeO HO

MeO

H

CH3

CH3

11-h

ydro

xy-1

,2,1

0-tr

imet

hoxy

-6,6

-dim

ethy

l-5,6

,6a,7

-tetr

ahyd

ro-4H

-di

benz

o[de

,g]qu

inol

in-6

-ium

Colum

bamine

C 20H20NO4

+338.38

g/mol

N+

O

O

OH

O

2-hy

drox

y-3,

9,10

-trim

etho

xy-5

,6-d

ihyd

roiso

quin

olin

o[3,

2-a]

isoqu

inol

in-7

-ium

Nilo

ticin

acetate

C 32H50O4

498.75

g/mol

O

H

H

O

O

O

Nilo

ticin

acet

ate

PiscidinolA

C 30H50O4

474.73

g/mol

OH O

H

HO

O

Pisc

idin

ol A

Quinica

cid

Chlorogenica

cid

C 16H18O9

354.31g/mol

OH

HO

O

HO

O

OH

O

OH

OH

Chlo

roge

nic A

cid

Neo-chlorogenicacid

C 16H18O9

354.31g/mol

HO

HO

O

O

OH

HO

OH

O

OH

Neo

chlo

roge

nic A

cid

3-O-fe

ruloylqu

inicacid

C 17H20O9

368.34

g/mol

O

O

O

abs

abs

abs

abs

HO

OH

O

OH

OH

HO

3-O

-Fer

uloy

lqui

nic a

cid

4-O-fe

ruloylqu

inicacid

C 17H20O9

368.34

g/mol

HHO

O

HO

OH

OH

OH

O

O

OH

(E)-

1,3,

5-tr

ihyd

roxy

-4-(

(3-(

4-hy

drox

y-3-

met

hoxy

phen

yl)a

cryl

oyl)o

xy)c

yclo

hexa

ne-

1-ca

rbox

ylic

acid

Evidence-Based Complementary and Alternative Medicine 15

Table3:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

5-O-fe

ruloylqu

inicacid

C 17H20O9

368.34

g/mol

O

HO

O

O

OH

O

HO

OH

OH

(1R,

3R,4S,

5R)-

1,3,

4-tr

ihyd

roxy

-5-(

(3-(

4-hy

drox

y-3-

met

hoxy

phen

yl)a

cryl

oyl)o

xy)c

yclo

hexa

ne-1

-ca

rbox

ylic

acid

Hydroxycinn

amicacid

CaffeicA

cidMethylE

ster

C 10H10O4

194.19

g/mol

HO

HO

O

O

Caffe

ic A

cid

Met

hyl E

ster

Phenolicacid

Ferulic

acid

C 10H10O4

194.19

g/mol

O

HO

O

OH

Feru

lic ac

id

Methylferulate

C 11H12O4

208.21g/mol

OH

OCH

3

OCH

3

O

met

hyl (E)

-3-(

4-hy

drox

y-3-

met

hoxy

phen

yl)a

cryl

ate

Protocatechu

icacid

C 7H6O4

154.12g/mol

COO

H

OH

OH

3,4-

dihy

drox

yben

zoic

acid

Lign

an(+/-)-5,5�耠-dim

etho

xylaric

iresin

ol-4-O

-glucosid

eC 28H38O13

582.6g/mol

O

HO

H2C

H3C

O

OCH

3

OCH

3

OH

OCH

3

OCI

G

(+/-

)-5,

5'-di

met

hoxy

laric

iresin

ol-4

-O-g

luco

side

Syrin

garesin

oldi-O

-𝛽-D

-glucopyrano

side

C 33H44O18

728.70

g/mol

OH

OH

OH

OH

OH

OO

O

O

OO

HH

(2R,

3R,4R,

5S,6R)

-6-(

4-((

1S,3

aR,4S,

6aR)

-4-(

3,5-

dim

etho

xy-4

-(((

2S,3R,

4S,5S,

6R)-

3,4,

5-tr

ihyd

roxy

-6-

(hyd

roxy

met

hyl)t

etra

hydr

o-2H

-pyr

an-2

-yl)o

xy)p

heny

l)tet

rahy

dro-

1H,3H

-furo

[3,4

-c]fu

ran-

l-yl)-

2,6-

dim

etho

xyph

enox

y)te

trah

ydro

-2H

-pyr

an-2

,3,4

,5-te

trao

l

HO

HO HO

OM

e

OM

e

OM

e

MeO

16 Evidence-Based Complementary and Alternative Medicine

Table3:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

(-)-syrin

garesin

olC 22H26O8

418.44

g/mol

HO

OCH

3

H3C

OO O

HH

OCH

3

OH

OCH

3

4,4'-

((1R

,3aS

,4R,

6aS)

-tetr

ahyd

ro-1H

,3H

-furo

[3,4

-c]fu

ran-

1,4-

diyl

)bis(

2,6-

dim

etho

xyph

enol

)

Cou

marin

3-acetyl-3,4-dihydro-5,6-dim

etho

xy-1H-2-benzopyran-

1-one

C 13H14O5

250.25

g/mol

O

H3C

O

OCH

3

O

O

3-ac

etyl

-5,6

-dim

etho

xyiso

chro

man

-1-o

ne

Paraben

N-propylp

araben

C 10H12O3

180.20

g/mol

OH

O O

prop

yl 4

-hyd

roxy

benz

oate

Phenoliclacton

ePh

ellolacton

eC 13H14O8

298.25

g/mol

OCH

3

OH

OO

OH

OH

O

O

((3R

,4R)

-3,4

-dih

ydro

xy-5

-oxo

tetr

ahyd

rofu

ran-

3-yl

)met

hyl 4

-hyd

roxy

-3-

met

hoxy

benz

oate

Ferulate

N-butylFerulate

C 14H18O4

250.29

g/mol

OCH

3

HO

CH2C

H2C

H2C

H3O

O

(E)-

4-(3

,7-d

ioxo

-7-h

ept-1

-en-

1-yl

)-1-

hydr

oxy-

2-m

etho

xybe

nzen

e6

Amurenlacton

eAC 17H20O9

368.34

g/mol

OH

OCH

3

O

O

OH

OO

H3C

OO

H

(R)-

2-hy

drox

y-2-

((2S

,3S,

4R)-

4-hy

drox

y-3-

met

hoxy

-5-o

xote

trah

ydro

fura

n-2-

yl)e

thyl

(E)-

3-(4

-hyd

roxy

-3-

met

hoxy

phen

yl)a

cryl

ate

Hydroxybenzaldehyde

4-hydroxybenzaldehyde

C 7H8O2

124.14g/mol

CHO

H3

OH

4-hy

drox

yben

zald

ehyd

e com

poun

d w

ith d

ihyd

roge

n (1

:1)

Evidence-Based Complementary and Alternative Medicine 17

Table3:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Phenolicaldehyde

Vanillin

C 8H8O3

152.15g/mol

OH

OCH

3

CHO

4-hy

drox

y-3-

met

hoxy

benz

alde

hyde

Glycosid

e3,4,5-trim

etoxypheno

lO-𝛽-D

-glucopyrano

side

C 9H11O3

167.18g

/mol

OCH

3

H3C

OO

CH3

O-g

lc

3,4,

5-Tr

imet

hoxy

phen

ol O

-ß-D

-glu

copy

rano

side

2-metho

xy-4-(2-prop

enyl)phenyl-b

eta-D-

glucop

yranoside

C 16H22O7

326.35

g/mol

O OH

OH

HO

OH

O

O

2-m

etho

xy-4

-(2-

prop

enyl

)phe

nyl-b

eta-

D-g

luco

pyra

nosid

e

2-(p-hydroxyph

enyl)-ethano

l-1-O

-𝛽-D

-apiofuranosyl

(1–6

)-O-𝛽-D

-glucopyrano

side

C 9H12O

136.19g/mol

OH

OA

PI(1

6)

glu

2-(p

-hyd

roxy

phen

yl)-

etha

nol-1

-O-b

eta-

D-a

piof

uran

osyl

(1-6

)-O

-bet

a-D

-glu

copy

rano

side

3,5-dihydroxybenzoicacid-O

-xylop

yranosyl-

glucop

yranoside

C 8H8O3

152.15g/mol

OHO

XyI-

GIc

HO

OC

3, 5

-dih

ydro

xybe

nzoi

caci

d-O

-xyl

opyr

anos

yl-g

luco

pyra

nosid

e

18 Evidence-Based Complementary and Alternative Medicine

Table3:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Phenolicglycoside

Tachiosid

eC 12H16O8

288.25

g/mol

OOO

H

O

HO

OH

HO

OH

(2S,

3S,4S,

5R,6R)

-6-(

4-hy

drox

y-3-

met

hoxy

phen

oxy)

tetr

ahyd

ro-2H

-pyr

an-

2,3,

4,5-

tetr

aol

Glucosid

eSalid

rosid

eC 14H20O7

300.31g/mol

OO

OH

HO

OH

OH

OH

(2R,

3S,4S,

5R,6R)

-2-(

hydr

oxym

ethy

l)-6-

(4-h

ydro

xyph

enet

hoxy

)tetr

ahyd

ro-2H

-pyr

an-3

,4,5

-trio

l

4-Hydroxybenzylalcoho

lC 7

H8O2

124.14

g/mol

OH

OH

4-(h

ydro

xym

ethy

l)phe

nol

Phenol

MethylSyringate

C 10H12O5

212.20

g/mol

OH

OO

OO

met

hyl 4

-hyd

roxy

-3,5

-dim

etho

xybe

nzoa

te

Dehydrovomifo

liol

(6S)-dehydrovomifo

liol

C 13H18O3

222.28

g/mol

H3C

H3C

CH3

OH

H3C

OO

(S,E

)-4-

hydr

oxy-

3,5,

5-tr

imet

hyl-4

-(3-

oxob

ut-1

-en-

1-yl

)cyc

lohe

x-2-

en-1

-one

(6R,7aR)-epilolio

lide

C 11H16O3

196.25

g/mol

OO

H

CH3

H3C

CH3

O

(6S,

7aS)

-6-h

ydro

xy-4

,4,7

a-tr

imet

hyl-5

,6,7

,7a-

tetr

ahyd

robe

nzof

uran

-2(4H

)-on

e

Evidence-Based Complementary and Alternative Medicine 19

Table4:Molecular

form

ula,molecular

weight

andchem

icalstr

uctureso

fcom

poun

dsderiv

edfro

mPA

Cspecies(34

compo

unds).

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Alkaloid

Berberine

C 20H18NO4

+336.37

g/mol

O

O

N+

O

O

Berb

erin

e

Berberrubine

C 19H16NO4

+322.34

g/mol

N+

O

O

Berb

erru

bine

O

O

H

Berberastin

eC 20H18NO5

+352.37

g/mol

N+

O

O

OH

Berb

eras

tine

O

O

Δ7-D

ehydrosoph

oram

ine

C 15H18N2O

242.32

g/mol

N

N

O

H H

Delt

a-7-

dehy

dros

opho

ram

ine

Palm

atine

C 21H22NO4

+352.41g/mol

O

N+

O

O

O

Palm

atin

e

Tetrahydropalm

atine

C 21H25NO4

355.43

g/mol

N

O O

O O

Tetr

ahyd

ropa

lmat

ine

Phellodend

rine

C 20H24NO4

+342.41

g/mol

N+

H

O

HO

OH

O

Phel

lode

ndrin

e

Jatro

rrhizine

orNeprotin

,2,9,10-Trim

etho

xy-5,6-

dihydroisoqu

inolino[2,1-b

]isoq

uino

lin-7-iu

m-3-ol

C 20H19NO4

337.3

8g/m

olN

+

O- O

O O

Jatro

rrhi

zine

20 Evidence-Based Complementary and Alternative MedicineTa

ble4:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Lotusin

eC 19H24NO3

+314.40

g/mol

N+

HO

H3C

O

H

OH

CH3

CH3

(S)-

6-hy

drox

y-1-

(4-h

ydro

xybe

nzyl

)-7-

met

hoxy

-2,2

-dim

ethy

l-1,2

,3,4

-te

trah

ydro

isoqu

inol

in-2

-ium

Menisp

erine

C 21H26NO4

+356.44

g/mol

N+

H

H3C

O

MeO H

O

MeO

H

CH3

CH3

11-h

ydro

xy-1

,2,1

0-tr

imet

hoxy

-6,6

-dim

ethy

l-5,6

,6a,7

-tetr

ahyd

ro-4H

-di

benz

o[de,g]

quin

olin

-6-iu

m

Isoq

uino

line

alkaloid

Arm

epavine

C 19H23NO3

313.40

g/mol

OH

NO O

Arm

epav

ine

Dem

ethyleneberberine

C 19H18NO4

+324.36

g/mol

OO

N+

OH

OH

Dem

ethy

lene

berb

erin

e

Limon

oid

KihadaninB

C 26H30O9

486.52

g/mol

abs

abs

abs

O

Oab

s

O

abs

abs

abs

OO

Oab

s

O

O

HO

Kiha

dani

n B

Nilo

ticin

C 30H48O3

456.71g/mol

OH

O

O

Nilo

ticin

Obaculacton

eorlim

onin

C 26H30O8

470.52

g/mol

O

OO

O

O

O

O

O

H

H

limon

in

Obacuno

neor

Obacuno

icacid

C 26H30O7

454.52

g/mol

O

O

O

O

O

H

HO

O

Oba

cuno

ne

N-acylamines

Herculin

C 16H29NO

251.4

1g/m

ol

O

N H

(2E,

8E)-

N-(

2-m

ethy

lpro

pyl)d

odec

a-2,

8-di

enam

ide

Evidence-Based Complementary and Alternative Medicine 21

Table4:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Phenolicacid

Ferulic

acid

C 10H10O4

194.19

g/mol

O

HO

O

OH

Feru

lic A

cid

Quinica

cid

Quinica

cid

C 7H12O6

192.17g/mol

HO

OH

OH

HOO

OH

Qui

nic a

cid

3-O-fe

ruloylqu

inicacid

or5-O-fe

ruloylqu

inicacid

C 17H20O9

368.34

g/mol

O

O

O

abs

abs

abs

abs

HO

OH

O

OH

OH

HO

3-O

-feru

loyl

quin

ic ac

id

Chlorogenica

cid

C 16H18O9

354.31g/mol

OH

HO

O

HO

O

OH

O

OH

OH

Chlo

roge

nic a

cid

Sanlengacid

C 18H34O5

330.47

g/mol

OH

OH

OH

O

OH

(E)-

6,9,

10-tr

ihyd

roxy

octa

dec-

7-en

oic a

cid

Phytosterol

𝛽-sito

sterol

C 29H50O

414.72

g/mol

HO

H

HH

H

Beta

-Sito

stero

l

Flavon

oid

Amurensin

C 26H30O12

534.51g/mol

OH

OO

HO

HO

OH

OH

OH

O

OH

O

OH

Am

uren

sin

Quercetin

C 15H10O7

302.24

g/mol

OH

OO

H

HO

O

OHOH

Que

rcet

in

22 Evidence-Based Complementary and Alternative Medicine

Table4:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Phellamurin

C 26H30O11

518.52

g/mol

O

O

O

O

OH

OH

HO

OH

HO

OH

HO

Phel

lam

urin

Phellatin

C 26H30O12

534.51g/mol

OO

O

O

HO

OH

OH

OH

OH

HO

OH

OH

3,5-

dihy

drox

y-6-

(3-h

ydro

xy-3

-met

hylb

utyl

)-2-

(4-h

ydro

xyph

enyl

)-7-

[(2S

,4S,

5S)-

3,4,

5-tr

ihyd

roxy

-6-

(hyd

roxy

met

hyl)o

xan-

2-yl

]oxy

chro

men

-4-o

ne

Phellavin

C 26H32O12

536.53

g/mol

OH

O

OH

OO

H

OO

HO

H2C

CH3

CH3

OH

OH

OH

OH

Phel

lavi

n

7-dehydrostig

masterol

C 29H50O

414.72

g/mol

H

H

OH

H

HH

(3S,

5S,9R,

10S,

13R,

14R,

17R)

-17-

((2R

,5S)

-5-e

thyl

-6-m

ethy

lhep

tan-

2-yl

)-10

,13-

dim

ethy

l-2,3

,4,5

,6,9

,10,

11,1

2,13

,14,

15,1

6,17

-tetr

adec

ahyd

ro-1H

-cy

clope

nta[a]

phen

anth

ren-

3-ol

Rutaceae

Noricariside

C 26H30O12

534.51g/mol

OH

O

OH

OO

H

OH

O

OH

OH

OH

OH

O

3,5,

7-tr

ihyd

roxy

-2-(

4-hy

drox

yphe

nyl)-

8-(3

-met

hyl-3

-(((

2S,3R,

4S,5S,

6R)-

3,4,

5-tr

ihyd

roxy

-6-

(hyd

roxy

met

hyl)t

etra

hydr

o-2H

-pyr

an-2

-yl)o

xy)b

utyl

)-4H

-chr

omen

-4-o

ne

Stigmastane

Phellodend

rosid

eC 26H30O11

518.52

g/mol

O

O

OO

O

OH

OH

OH

OH

OH

OH

5-hy

drox

y-2-

(4-h

ydro

xyph

enyl

)-8,

8-di

met

hyl-3

-[(2

S,3R

,4S,

5S,6

R)-3

,4,5

-trih

ydro

xy-6

-(h

ydro

xym

ethy

l)oxa

n-2-

yl]o

xy-2

,3,9

,10-

tetr

ahyd

ropy

rano

[2,3

-h]c

hrom

en-4

-one

Evidence-Based Complementary and Alternative Medicine 23

Table4:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Mon

osaccharide

Syrin

gin

C 17H24O9

372.37

g/mol

OO

OH

HO

OH

HO

OO

HHO

H

(2R,

3S,4S,

5R,6S)

-2-(

hydr

oxym

ethy

l)-6-

(4-(

(E)-

3-hy

drox

ypro

p-1-

en-1

-yl)-

2,6-

dim

etho

xyph

enox

y)te

trah

ydro

-2H

-pyr

an-3

,4,5

-trio

l

Daucoste

rol

C 34H58O6

562.83

g/mol

O

HO

OH

HO

O

OH

H

H

H

H

(2S,

3S,4S,

5R,6R)

-6-(

((3S

,8S,

9S,1

0R,1

3R,1

4S,1

7R)-

17-(

(2R,

5R)-

5-et

hyl-6

-met

hylh

epta

n-2-

yl)-

10,1

3-di

met

hyl-2

,3,4

,7,8

,9,1

0,11

,12,

13,1

4,15

,16,

17-te

trad

ecah

ydro

-1H

-cy

clope

nta[a]

phen

anth

ren-

3-yl

)oxy

)tetr

ahyd

ro-2H

-pyr

an-2

,3,4

,5-te

trao

l

Ferulate

Amurenam

ideA

C 17H25NO9

387.39g

/mol

H

HO

H OCH

3

H

H

O

HH

OH

H OH

OCH

3

NH

2

O

OO

HH

H

H

6-am

ino-

2,3,

5-tr

ihyd

roxy

-4-m

etho

xy-6

-oxo

hexy

l 3-(

4-hy

drox

y-3-

met

hoxy

phen

yl)p

ropa

noat

e

24 Evidence-Based Complementary and Alternative MedicineTa

ble5:Molecular

form

ula,molecular

weight

andchem

icalstr

uctureso

fcom

poun

dsderiv

edfro

mPA

Rspecies(84

compo

unds).

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Alkaloid

Berberine

C 20H18NO4

+336.37

g/mol

O

O

N+

O

O

Berb

erin

e

Bis-[4-(dimethylamino)ph

enyl]m

ethano

neC 17H20N2O

268.36

g/mol

NN

O

H3C

CH3

CH3

CH3

bis(

4-(d

imet

hyla

min

o)ph

enyl

)met

hano

ne

Dihydrocyclob

uxine-D

C 25H44N2O

388.64

g/mol

HN

CH3

CH3

CH3

OH

H3C

H3C

N HCH

3

2a,5

a,8-tr

imet

hyl-9

-(m

ethy

lam

ino)

-3-(

1-(m

ethy

lam

ino)

ethy

l)tet

rade

cahy

dro-

1H,1

2H-

cyclo

pent

a[a]

cyclo

prop

a[e]

phen

anth

ren-

4-ol

3,4-Dihydro-1-

[(4-hydroxyphenyl)m

ethyl]-7-metho

xy-

2-methyl-8

-isoq

uino

linol

C 20H24NO4

+342.41

g/mol

N+

O

OH

HO O

1,11

-dih

ydro

xy-2

,10-

dim

etho

xy-6

,6-d

imet

hyl-5

,6,6

a,7-te

trah

ydro

-4H

-di

benz

o[de

,g]qu

inol

in-6

-ium

3,4-Dihydro-1-

[(4-hydroxyphenyl)m

ethyl]-7-metho

xy-

2-methyl-6

-isoq

uino

linol

C 20H17NO5

351.3

6g/m

olN

O OO

OO

8,9-

dim

etho

xy-1

1,12

-dih

ydro

-14H

-[1,

3]di

oxol

o[4,

5-h]

isoqu

inol

ino[

2,1-b]

isoqu

inol

in-1

4-on

e

7,8-D

ihydroxyrutaecarpine

C 18H13N3O3

319.3

2g/m

olN

N N

OH

H

O

(7R)

-7,8

-dih

ydro

xy-8

,13-

dihy

droi

ndol

o[2',

3':3,

4]py

rido[

2,1-b]

quin

azol

in-5

(7H

)-on

e

4-Dim

ethylamino-4-is

opropylbenzene

C 18H22NO+

268.38

g/mol

+ H NCH

3

CH3

O

H3C

CH3

4-(4

-isop

ropy

lben

zoyl

)-N

,N-d

imet

hylb

enze

nam

iniu

m

Evod

iamine

C 19H17N3O

303.37

g/mol

N H

N N

H3C

O

14-m

ethy

l-8,1

3,13

b,14

-tetr

ahyd

roin

dolo

[2',3

':3,4

]pyr

ido[

2,1-b]

quin

azol

in-5

(7H

)-on

e

Evidence-Based Complementary and Alternative Medicine 25

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Palm

atine

C 21H22NO4

+352.41g/mol

ON

+

O

O

O

Palm

atin

e

Pteleine

C 13H13NO3

231.2

5g/m

olN

O

H3C

O

OCH

3

4,6-

dim

etho

xy-4

a,8a-

dihy

drof

uro[

2,3-b]

quin

olin

e

(-)-(R)-platydesmin

C 15H19NO3

261.3

2g/m

olN

O

OH

OCH

3

2-((

2R)-

4-m

etho

xy-2

,3,4

a,8a-

tetr

ahyd

rofu

ro[2

,3-b

]qui

nolin

-2-y

l)pro

pan-

2-ol

Noroxyhydrastinine

C 10H9NO3

191.19g

/mol

NH

O O

O

7,8-

dihy

dro-

[1,3

]dio

xolo

[4,5

-g]is

oqui

nolin

-5(6H

)-on

e

Chilenine

C 19H15NO7

369.3

3g/m

olN

O

O

OH

O

O

OO

11b-

hydr

oxy-

8,9-

dim

etho

xy-[

1,3]

diox

olo[

4,5-g]

isoin

dolo

[2,1

-b]is

oqui

nolin

e-7,

12(5H

,11bH

)-di

one

Phellodend

rine

C 20H24NO4

+342.41

g/mol

N+H

OHO

OH

O

Phel

lode

ndrin

e

Magno

curarin

eC 19H24NO3

+314.40

g/mol

N+

H3C

O HO

H

OH

CH3

etha

ne

7-hy

drox

y-1-

(4-h

ydro

xybe

nzyl

)-6-

met

hoxy

-2,2

-dim

ethy

l-1,2

,3,4

-tetr

ahyd

roiso

quin

olin

-2-iu

m

26 Evidence-Based Complementary and Alternative Medicine

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Magno

florin

eC 20H24NO4

+342.41

g/mol

N+

HO

HOO O

Mag

noflo

rine

Jatro

rrhizine

orNeprotin

,2,9,10-Trim

etho

xy-5,6-

dihydroisoqu

inolino[2,1-b

]isoq

uino

lin-7-iu

m-3-ol

C 20H19NO4

+337.3

8g/m

olN

+

O- O

O O

Jatro

rrhi

zine

13-M

etho

xyjatro

rrhizine

C 21H22NO5

+368.41

g/mol

N+

HO

H3C

O

H3C

OO

CH3

H

OCH

3

3-hy

drox

y-2,

9,10

,13-

tetr

amet

hoxy

-5,6

-dih

ydro

isoqu

inol

ino[

3,2-a]

isoqu

inol

in-7

-ium

�-Fagarine

C 13H11NO3

229.2

4g/m

olN

O

O

O

Gam

ma-

Faga

rine

Canthin-6-one

C 14H8N2O

220.23

g/mol

N

N

O

Cant

hin-

6-on

e

4-Metho

xy-N

-methyl-2

-quino

lone

C 11H11NO2

189.2

1g/m

olN

O

OCH

3

CH3

4-M

etho

xy-N

-met

hyl-2

-qui

nolo

ne

Candicine

C 10H16NO+

166.24

g/mol

OH

N+

CH3

CH3

CH3

1-(4

-hyd

roxy

phen

yl)-N

,N,N

-trim

ethy

lmet

hana

min

ium

Evidence-Based Complementary and Alternative Medicine 27

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Lotusin

eC 19H24NO3

+314.40

g/mol

N+

HO

H3C

O

H

OH

CH3

CH3

(S)-

6-hy

drox

y-1-

(4-h

ydro

xybe

nzyl

)-7-

met

hoxy

-2,2

-dim

ethy

l-1,2

,3,4

-te

trah

ydro

isoqu

inol

in-2

-ium

N-M

ethylhigenam

ine-7-O-glucopyrano

side

C 17H20N2O

268.36

g/mol

O

NN

bis(

4-(d

imet

hyla

min

o)ph

enyl

)met

hano

ne

N-m

ethylhigenam

ine-7-O-𝛽-D

-glucopyrano

side

N/A

N/A

N

OH

OCI

GCH

3

OH

N-m

ethy

lhig

enam

ine-

7-O

-bet

a-D

-glu

copy

rano

side

(−)-Oblon

gine

C 19H24NO3

+314.40

g/mol

N+

H

H3C

O

OH

OH

CH3

CH3

(S)-

8-hy

drox

y-1-

(4-h

ydro

xybe

nzyl

)-7-

met

hoxy

-2,2

-dim

ethy

l-1,2

,3,4

-tetr

ahyd

roiso

quin

olin

-2-

ium

Isom

er-of-b

erberin

eN/A

Isom

er-of-m

agno

florin

eIsom

er-of-p

almatine

Tetrahydroretic

uline

C 19H22NO4

+328.39

g/mol

OH

H3C

O

N+

H3C

O HO

CH3

7-hy

drox

y-1-

(3-h

ydro

xy-4

-met

hoxy

benz

yl)-

6-m

etho

xy-2

-met

hyl-3

,4-d

ihyd

roiso

quin

olin

-2-iu

m

Tetrahydrojatro

rrhizine

C 20H23NO4

341.4

1g/m

olN

OH

O

O

O

2,9,

10-tr

imet

hoxy

-6,8

,13,

13a-

tetr

ahyd

ro-5

H-is

oqui

nolin

o[2,

1-b]

isoqu

inol

in-3

-ol

Menisp

erine

C 21H26NO4

+356.44

g/mol

N+

H

H3C

O

MeO H

O

MeO

H

CH3

CH3

11-h

ydro

xy-1

,2,1

0-tr

imet

hoxy

-6,6

-dim

ethy

l-5,6

,6a,7

-tetr

ahyd

ro-4H

-di

benz

o[de

,g]qu

inol

in-6

-ium

28 Evidence-Based Complementary and Alternative Medicine

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

(+)N

-methylcorydine

C 21H26NO4

+356.44

g/mol

N+

H3C

O

HO

MeO

MeO

HH

CH3

CH3

1-hy

drox

y-2,

10,1

1-tr

imet

hoxy

-6,6

-dim

ethy

l-5,6

,6a,7

-te

trah

ydro

-4H

-dib

enzo

[de,g

]qui

nolin

-6-iu

m

N-M

ethylTetrahydrop

almatine

C 22H28NO4

+370.47

g/mol

N+

H3C

O

H3C

O

CH3

OCH

3

OCH

3

H

2,3,

9,10

-tetr

amet

hoxy

-7-m

ethy

l-5,6

,7,8

,13,

13a-

hexa

hydr

oiso

quin

olin

o[3,

2-a]

isoqu

inol

in-

7-iu

m

N-M

ethylflindersine

C 15H15NO2

241.2

9g/m

olNO

OCH3

CH3 CH

3

2,2,

6-tr

imet

hyl-2

,6-d

ihyd

ro-5H

-pyr

ano[

3,2-c]

quin

olin

-5-o

ne

Litcub

ine

C 19H22NO4

+328.39

g/mol

N+

OH

HO

O

O

3,10

-dim

etho

xy-7

-met

hyl-5

,6,1

2,12

a-te

trah

ydro

indo

lo[2

,1-a

]isoq

uino

lin-7

-ium

-2,9

-dio

lCa

utio

n: A

net

char

ge ap

pear

s to

be p

rese

nt

Hydroxyl-p

almatine

C 22H22O5

366.41g/mol

OM

e

OM

e

OH

MeO

MeO

Hyd

roxy

l-pal

mat

ine

11-Hydroxylpalmatine

C 21H22NO5

+368.41

g/mol

N+

H3C

O

H3C

O

HO

CH3

OCH

3

OH

11-h

ydro

xy-2

,3,9

,10-

tetr

amet

hoxy

-5,6

-dih

ydro

isoqu

inol

ino[

3,2-a]

isoqu

inol

in-7

-ium

Evidence-Based Complementary and Alternative Medicine 29

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

13-H

ydroxypalm

atine

C 21H22NO5

+368.41

g/mol

N+

OCH

3

OCH

3

H

HO

H3C

O

H3C

O

13-h

ydro

xy-2

,3,9

,10-

tetr

amet

hoxy

-5,6

-dih

ydro

isoqu

inol

ino[

3,2-a]

isoqu

inol

in-7

-ium

7-Hydroxy-8-m

etho

xydedihydrorutaecarpine

N/A

Tetrahydropalm

atine

C 21H25NO4

355.43

g/mol

N

O O

O OTe

trah

ydro

palm

atin

e

5,8,13,13

a-Tetrahydro-2,9,10,11-te

trahydroxy-3-

metho

xy-7-m

ethyl-6

H-dibenzo[a,g]quino

lizinium

C 21H20NO6

+382.39

g/mol

N+

OH

2CO

OH

2CO

OCH

3

O

H

-oxi

dane

yl)m

etho

xy)-

9,10

-dim

etho

xy-5

,6-d

ihyd

roiso

quin

olin

o[3,

2-a]

isoqu

inol

in-7

-ium

2,3-

bis(

( 1

Tetrahydroberberine

C 20H21NO4

339.3

9g/m

ol

N

O

O

O

O

9,10

-dim

etho

xy-5

,8,1

3,13

a-te

trah

ydro

-6H

-[1,

3]di

oxol

o[4,

5-g]

isoqu

inol

ino[

3,2-

a]iso

quin

olin

e

Xantho

planine

C 21H26NO4

+356.44

g/mol

O ON

+

H

OH

O

Xant

hopl

anin

e

N-m

ethylpho

ebine

C 22H26NO5

+384.45

g/mol

N+

OM

e

H3C

O

MeO H

CH3

CH3

OH

2CO

form

alde

hyde

, 1,2

,3-tr

imet

hoxy

-6,6

-dim

ethy

l-5,6

,6a,7

-tetr

ahyd

ro-4H

- be

nzo[de

]oxi

reno

[2',3

':4,5

]ben

zo[1

,2-g

]qui

nolin

-6-iu

m sa

lt

30 Evidence-Based Complementary and Alternative Medicine

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Colum

bamine

C 20H20NO4

+338.38

g/mol

N+

OH

O

O

O

3,9,

10-tr

imet

hoxy

-5,6

-dih

ydro

isoqu

inol

ino[

2,1-

b]iso

quin

olin

-7-iu

m-2

-ol

Caut

ion:

A n

et ch

arge

appe

ars t

o be

pre

sent

Dihydroxyl-jatrorrhizine

N/A

Epiberberin

eC 20H18NO4

+336.37

g/mol

O

O

N+

O

O

Epib

erbe

rine

Rutecarpine

C 18H13N3O

287.32g

/mol

N

N

N

H

O

8,13

-dih

ydro

indo

lo[2

',3':3

,4]p

yrid

o[2,

1-b]

quin

azol

in-5

(7H

)-on

e

Skim

mianine

C 14H14NO4

+260.27

g/mol

N H +

O

OCH

3

H3C

O

OCH

3

4,7,

8-tr

imet

hoxy

furo

[2,3

-b]q

uino

lin-9

-ium

Tembetarin

eC 21H22NO4

+352.41g/mol

N+

H3C

O

H3C

O

OCH

3

O

H

2,3,

9,10

-tetr

amet

hoxy

-5,6

-dih

ydro

isoqu

inol

ino[

3,2-a]

isoqu

inol

in-7

-ium

8-Oxoberberine

C 20H17NO5

351.3

6g/m

ol

N

O O

OM

e

OM

e

O

9,10

-dim

etho

xy-5

,6-d

ihyd

ro-8H

-[1,

3]di

oxol

o[4,

5-g]

isoqu

inol

ino[

3,2-a]

isoqu

inol

in-8

-one

Evidence-Based Complementary and Alternative Medicine 31

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

8-Oxoepiberberin

eC 20H17NO5

351.3

6g/m

olN

H3C

O

H3C

O

O

OO

H+

hydr

ogen

catio

n

prop

ane

8,9-

dim

etho

xy-1

1,12

-dih

ydro

-14H

-[1,

3]di

oxol

o[4,

5-h]

isoqu

inol

ino[

2,1-b]

isoqu

inol

in-1

4-on

e

8-Oxopalm

atine

C 21H21NO5

367.4

0g/m

olN

H3C

O

H3C

O

OCH

3

OCH

3

O

H+

hydr

ogen

catio

n

prop

ane

2,3,

9,10

-tetr

amet

hoxy

-5,6

-dih

ydro

-8H

-isoq

uino

lino[

3,2-a]

isoqu

inol

in-8

-one

Oxyberberine

C 20H17NO5

351.3

6g/m

ol

N

O O

OCH

3

OCH

3

O

9,10

-dim

etho

xy-5

,6-d

ihyd

ro-8H

-[1,

3]di

oxol

o[4,

5-g]

isoqu

inol

ino[

3,2-

a]iso

quin

olin

-8-o

ne

Oxypalm

atine

C 21H21NO5

367.4

0g/m

ol

O

O

O

Oxy

palm

atin

eO

ON

Limon

oid

Obaculacton

eorlim

onin

C 26H30O8

470.52

g/mol

O

OO

O

O

O

O

O

H

H

limon

in

Obacuno

neor

Obacuno

icacid

C 26H30O7

454.52

g/mol

O

O

O

O

O

H

HO

O

Oba

cuno

ne

32 Evidence-Based Complementary and Alternative Medicine

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

12𝛼-hydroxylim

onin

C 26H30O9

470.52

g/mol

O

O

O

OH

OO

O

O

O

12-a

lpha

-Hyd

roxy

limon

in

Rutaevin

C 26H30O9

486.52

g/mol

O

OH

O

HO

OHO

O

O

H

O

Ruta

evin

Con

iferin

C 16H22O8

342.34

g/mol

OH

O

O

O

OH

OH

HO

HO

Con

iferin

Vanillo

losid

eC 14H20O8

316.31g/mol

H3C

O

OCI

GCH

2OH

Vani

llolo

side

Phenolicacid

2-(p-hydroxyph

enyl)-ethano

l-1-O

-𝛽-D

-apiofuranosyl

(1–6

)-O-𝛽-D

-glucopyrano

side

C 9H12O

136.19g/mol

OH

OA

PI(1

6)

glu

2-(p

-hyd

roxy

phen

yl)-

etha

nol-1

-O-b

eta-

D-a

piof

uran

osyl

(1-6

)-O

-bet

a-D

-glu

copy

rano

side

3,5-dihydroxybenzoicacid-O

-xylop

yranosyl-

glucop

yranoside

C 8H8O3

152.15g/mol

OHO

XyI-

GIc

HO

OC

3, 5

-dih

ydro

xybe

nzoi

caci

d-O

-xyl

opyr

anos

yl-g

luco

pyra

nosid

e

Evidence-Based Complementary and Alternative Medicine 33

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Ferulic

acid

C 10H10O4

194.19g/mol

O HO

O

OH

Feru

lic ac

id

Quinica

cid

Neochlorogenica

cid

C 16H18O9

354.31g/mol

HO

HO

O

O

OH

HO

OH

O

OH

Neo

chlo

roge

nic A

cid

3-O-fe

ruloylqu

inicacid

or5-O-fe

ruloylqu

inicacid

C 17H20O9

368.34

g/mol

O

O

O

abs

abs

abs

abs

HO

OH

O

OH

OH

HO

3-O

-Fer

uloy

lqui

nic a

cid

Chlorogenica

cid

C 16H18O9

354.31g/mol

OH

HO

O

HO

O

OH

O

OH

OH

Chlo

roge

nic A

cid

Methyl3-O

-feruloylqu

inate

C 18H22O9

382.37

g/mol

COO

CH3

OH

OFe

rulo

yl

OH

OH

Met

hyl 3

-O-fe

rulo

ylqu

inat

e

Methyl5-O

-feruloylqu

inate

C 8H13O6

205.19g/mol

OH

OO

CMe

O

OH

HO

Feru

loyl

Met

hyl 5

-O-fe

rulo

ylqu

inat

e

34 Evidence-Based Complementary and Alternative MedicineTa

ble5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

3-Feruoyl-4

-caffeoylqu

inicacid

C 26H26O12

530.48

g/mol

COO

H

OH

OFe

rulo

yl

OCa

ffelo

yl

OH

3-Fe

ruoy

l-4-c

affeo

ylqu

inic

acid

Lign

an(+/-)-lyon

iresin

olC 22H28O8

420.46

g/mol

CH2O

HH

3CO

OH

OCH

3

CH2O

H

H3C

O

OH

OCH

3

((1S

,2R,

3R)-

7-hy

drox

y-1-

(4-h

ydro

xy-3

,5-d

imet

hoxy

phen

yl)-

6,8-

dim

etho

xy-1

,2,3

,4-te

trah

ydro

naph

thal

ene-

2,3-

diyl

)dim

etha

nol

(+/-)-5,5�耠-

dimetho

xylaric

iresin

ol-4-O

-glucosid

eC 28H38O13

582.6g

/mol

O

HO

H2C

H3C

O

OCH

3

OCH

3

OH

OCH

3

OCI

G

(+/-

)-5,

5'-di

met

hoxy

laric

iresin

ol-4

-O-g

luco

side

Syrin

garesin

oldi-O

-𝛽-D

-glucopyrano

side

C 33H44O18

728.70

g/mol

O

O

O

O

O

O

HO

HO

HO

OH

OH

OH

OH

OH

OM

e

OM

e

OM

e

(2R,

3R,4R,

5S,6R)

-6-(

4-((

1S,3

aR,4S,

6aR)

-4-(

3,5-

dim

etho

xy-4

-(((

2S,3R,

4S,5S,

6R)-

3,4,

5-tr

ihyd

roxy

-6-

(hyd

roxy

met

hyl)t

etra

hydr

o-2H

-pyr

an-2

-yl)o

xy)p

heny

l)tet

rahy

dro-

1H,3H

-furo

[3,4

-c]fu

ran-

1-yl

)-2,

6-di

met

hoxy

phen

oxy)

tetr

ahyd

ro-2H

-pyr

an-2

,3,4

,5-te

trao

l

HH

MeO

Flavon

oid

𝛽-anh

ydrono

ricaritin

N/A

Icariside-1

C 26H28O11

516.50

g/mol

OO

O

OH

HO

O

HO

OH

HO

OH

O

3,5-

dihy

drox

y-2-

(4-m

etho

xyph

enyl

)-8-

(3-m

ethy

lbut

-2-e

n-1-

yl)-

7-((

(2R,

3R,4S,

5S,6S)

-3,4

,5,6

-te

trah

ydro

xyte

trah

ydro

-2H

-pyr

an-2

-yl)o

xy)-

4H-c

hrom

en-4

-one

Phellamuretin

C 20H20O6

356.37

g/mol

OO

HO

OH

HO

O

(2R,

3R)-

3,5-

dihy

drox

y-2-

(4-h

ydro

xyph

enyl

)-8,

8-di

met

hyl-2

,3,9

,10-

tetr

ahyd

ro-4H

,8H

-pyr

ano[

2,3-

f]chr

omen

-4-o

ne

Evidence-Based Complementary and Alternative Medicine 35

Table5:Con

tinued.

Com

poun

dderiv

atives

Com

poun

dMolecular

form

ula

Molecular

weight

Chem

icalstr

uctures

Phellosid

eC 31H40Cr

O17

736.64

g/mol

O

CH2O

H

HO

OH

OCr CH

2

CH3

H3C

OH

CH2

O

OH

OH

HO

O

O

O

OH

OH

OH

HO

H2C

(2-(

3,5-

dihy

drox

y-2-

(4-h

ydro

xyph

enyl

)-4-

oxo-

7-((

(3R,

4S,5S,

6R)-

3,4,

5-tr

ihyd

roxy

-6-

(hyd

roxy

met

hyl)t

etra

hydr

o-2H

-pyr

an-2

-yl)o

xy)-

4H-c

hrom

en-8

-yl

)eth

yl)d

imet

hyl((

(3R,

4S,5S,

6R)-

3,4,

5-tr

ihyd

roxy

-6-(

hydr

oxym

ethy

l)tet

rahy

dro-

2H-p

yran

-2-

yl)o

xy)c

hrom

ium

Dihydroph

ellosid

eC 31H44Cr

O17

740.67

g/mol

O

OCr

CH2O

H

OH

OH

OH

CH3

H3C

CH2

CH2

O

OH

O

OH

OH

O

O

OH

OH

OH

HO

H2C

(2-(

3,5-

dihy

drox

y-2-

(4-h

ydro

xycy

clohe

xa-1

,3-d

ien-

1-yl

)-4-

oxo-

7-((

(3R,

4S,5S,

6R)-

3,4,

5-tr

ihyd

roxy

-6-(

hydr

oxym

ethy

l)tet

rahy

dro-

2H-p

yran

-2-y

l)oxy

)chr

oman

-8-

yl)e

thyl

)dim

ethy

l(((3R,

4S,5S,

6R)-

3,4,

5-tr

ihyd

roxy

-6-(

hydr

oxym

ethy

l)tet

rahy

dro-

2H-

pyra

n-2-

yl)o

xy)c

hrom

ium

Isovalericacid

C 5H10O2

102.13g/mol

OH

O

3-m

ethy

lbut

anoi

c aci

d

Kaem

pferol

C 15H10O6

286.24

g/mol

O

OH

HO

OH

O

OH

3,5,

7-tr

ihyd

roxy

-2-(

4-hy

drox

yphe

nyl)-

4H-c

hrom

en-4

-one

D-glucose

C 6H12O6

180.16

g/mol

O OH

HO

OH

OH

OH

(3R,

4S,5S,

6R)-

6-(h

ydro

xym

ethy

l)tet

rahy

dro-

2H-p

yran

-2,3

,4,5

-tetr

aol

Paraben

N-propylp

araben

C 10H12O3

180.20

g/mol

OH

O O

prop

yl 4

-hyd

roxy

benz

oate

Glycosid

eSinapylaldehyde-4-O-beta-D-glucopyrano

side

C 13H14O6

266.25

g/mol

MeO

Glc

O

OM

e

CHO

(E)-

2,6-

dim

etho

xy-4

-(3-

oxop

rop-

1-en

-1-y

l)phe

nyl 2

-hyd

roxy

acet

ate

36 Evidence-Based Complementary and Alternative Medicine

multimedication resistant P. aeruginosa strains.The extract ofPCS significantly downregulated minimal inhibitory concen-trations (MICs) of amikacin and gentamicin in the two mul-timedication resistant P. aeruginosa strains [38]. PC showedits potential on the inhibition of Propionibacterium acnesstrains. Its MIC

50and MIC

90were 24𝜇g/ml and 190𝜇g/ml,

respectively [39]. For fungal infections, the monomers ofPC showed antifungal activity through compromising theintegrity of fungal cell wall and cell membrane and increasingthe expressions of energy metabolic genes. Therefore thelife expectancy of Microsporum Canis is shortened. Fur-thermore, the mingling use of palmatine hydrochloride andberberine hydrochloride could effectively treat MicrosporumCanis induced dermatomycosis in rabbit [40]. For virusinfections, the ethanol extract of PAR exerted moderateeffect against Herpes Simplex Virus by either interruptingvirion envelope structures or disguising as indispensable viralcompounds for absorption or infiltration of host cells [33].Another study had proved that PAR has a broad spectrum offunctions against virus-like VSV-GFP, PR8-GFP, NDV-GFP,HSV-GSP, H3-GFP, and EV-71 in vitro and also has effects ondifferent strains of influenza A such as H1N1, H5N2, H7N3,and H9N2 in vivo mice model [41].

5.3. Antitumor Effects. There are 3 compounds in PCS thathave been found to resist three types of tumours which in-cluded leukemic cell lines K562 and HEL, breast cancer cellline MDA, and prostate cancer cell line PC3. The compound[(21S, 23R) epoxy-24-hydroxy-21𝛽, 25-diethoxy] tirucalla-7-en-3-one has a relatively strong effect as Adriamycin againstfour tumors with the measurement of IC

50; toonaciliatin K

and piscidinol A have a comparably moderate effect in thisregard [42]. There are 9 most effective compounds of PCfor prostate cancer, namely, magnoflorine-O-glucuronide, (p-hy-droxybenzyl)-6, 7-dihydroxy-N-methyl tetrahydro iso-quinoline-7-O-p-D-glucopyranosid, magnoflorine, menisper-ine-O-glucuronide, menisperine, berberine, Jatrorrhizine,obaculactone, and obacunone [43]. Polysaccharides from anaqueous extract of PCS act on cell-mediated stimulationand humoral immunity instead of tumor cell inhibition toexert tumoricidal activity. Specifically, some polysaccharidesstimulate macrophages and NK cells via 𝛽-glucan-bindinglectin site of complement receptor type 3 [44].

5.4. Antigout Effects. Si-Miao-Wan (SMW) formula had beenproved to be effective for gout and gouty arthritis. Inthis formula, PC is the monarch herb which is the coreingredient to guide the other three herbs indicating that thealkaloids and organic acids in PC are the potential com-pounds for SMW. Alkaloids include candicine, oblongine,phellodendrine, tembetarine, magnoflorine, lotusine, n-methylterahydrocolumbamine, menisperine, noroxyhydras-tinine, demethyleneberberine, tetrahydropalmatine, oxyber-berine, armepavine, oxypalmatine, columbamine, jatror-rhizine, thalifendine, berberrubine, n-methyl canadine, pal-matine, berberine, obaculactone, obacunone, and amuren-laetone B, and organic acids include neochlorogenic acid,chlorogenic acid, cryptogenic acid, cryptochlorogenin acid,caffeoyl-CH

2-O-quinic acid, 3-O-feruloylqinic acid, ferulic

acid, and sanleng acid [45]. Er-Miao-Wan formula is amodified version of SMW, which had been elucidated for itschief ingredient PCSwhich exerts potent hypouricemic effect[46].

5.5. Antiulcer Effects. Peptic ulcers are associated with psy-chological stress and mental illness. Themiddle dosage of PCextract could significantly reduce the levels of serotonin in thebrain and noradrenaline in the adrenal gland. Both serotoninand noradrenaline take effect in the mental depression.Besides, for the molecule in PC, berberine has the ability toinhibit monoamine oxidase-A and modulate the brain nora-drenaline, serotonin, and dopamine levels [47]. Anotherstudy revealed that PC could protect the gastric mucosa byreinforcing the gastric mucosal barrier through endogenoussulfhydryl compounds and diethyldithiocarbamate-sensitivecompounds [48].

5.6. Antioxidant Effects. The antioxidant activity of PAR isproportional to its extract’s concentration. In another aspect,the ethanol extract exhibited a better antioxidant effectbecause of its high concentration of phenolics and flavonoidsthan aqueous extract [33]. Phellodendrine from PC couldplay an antioxidant role by modulating the AKT/NF-𝜅Bpathway in the zebrafish embryo. Besides, phellodendrinecould undo the expression of AKT and NF-𝜅B, IKK, andCOX-2 [49].

5.7. Sun Screening Effects. The sun screening effects of PChave been demonstrated through an experiment which wasdesigned for sun screening effect of 50% alcohol extracts of100 Chinese herbal medicines. The study showed PC couldabsorb 91.8% of ultraviolet-C, 79.1% of ultraviolet-B, and50.7% of ultraviolet-A. It is regarded as highly effective forsun screening if the absorption rate of ultraviolet is higherthan 90%. Therefore, PC could be a strong candidate forsunproof of ultraviolet-C [50]. Also, PC could also improveskin oxidative lesion induced by ultraviolet radiation viadecreasing lipid peroxidation and increasing antioxidantenzymes activities [51].

5.8. Other Effects. PC stimulates longitudinal bone growthand chondrocyte proliferation via upregulating bone mor-phogenetic protein-2 (BMP-2) and insulin-like growth factor(IGF-1) expression in the growth cartilage [52]. Besides, PCcould activate the fibrinogen system to take the hemostaticeffect. This validated charcoaled PC could stop bleeding[53]. The extract of PC also shows neuroprotective effectthrough adjusting the PC-12 cell apoptosiswhichwas inducedby 1-methyl-4-phenylpyridinium (MPP+) and hindered therelease of cytochrome C into the cytosol [54]. PAR couldease the symptoms of atopic dermatitis by decreasing thenumbers of mast cells, serum levels of TNF-𝛼, and INF- 𝛾and the expression levels of cytokines [56]. PAR could delayor even prevent the progression of diabetic nephropathy bycorrecting the high blood sugar state, antioxidant enzymesystem, and kidney malfunction and reversing histopatho-logical changes inflicted by diabetes on kidney [57]. Tofurther elaborate its mechanism on the compound level,

Evidence-Based Complementary and Alternative Medicine 37

berberine could attenuate the renal malfunction by inhibitingrenal aldose reductase and decreasing oxidative stress [58].Magnoflorine and phellodendrine could inhibit the immuneresponse by suppressing local graft versus host reactionand induction phase of picryl chloride-induced delayed-type hypersensitivity [59]. To counter asthma attack, theextract of PCS inhibits tracheal smooth muscle contractioninduced by high K+. Meanwhile, it could also block trachealsmooth muscle concentration induced by Nifedipine [6].Thepharmacological activities of PC and its related derivativeshave been listed in Table 6.

6. Pharmacokinetics

According to Chinese Pharmacopeia (Edition 2015), phel-lodendrine has been used as one of the evaluating indexesof PC. Phellodendrine could be rapidly absorbed in tissuessuch as plasma, liver, spleen, kidney, and brain. Besides,kidney is the major distribution tissue and the target organof phellodendrine. Furthermore, the experimental study onanimal suggested that this constituent has no long-termbuild-up effect on the tissues. Intriguingly, the extract ofphellodendrine could be found in the animal brain tissueindicating that this constituent may penetrate the commonmedication’s biggest hurdle: blood-brain barrier. The maxi-mum concentration time is at 5 minutes after intravenousadministration. The elimination half-life is no longer than2 hours [63]. Another constituent from PC is magnoflorinewhich shows low bioavailability and high absorption andelimination rates after oral and intravenous administration ofthis constituent in pure compound form.While its bioactivitycan be dramatically increased, absorption and eliminationrates can be significantly decreased after oral administra-tion of the PC decoction. Similarly, with oral administra-tion of mixture, magnoflorine (40mg/kg) and berberine(696.4mg/kg, the equivalent dosage in PC decoction), thebioavailability and absorption and elimination rates have asimilar trend. It suggested berberine plays an important rolein the drug-drug interaction with magnoflorine in the PCdecoction. On the other hand, these findings also warn usthat the mingling use of berberine andmagnoflorine possiblyincreases the risk of toxicity which possibly gives somesupport to the theory that herbalmedicinemay achieve bettertherapeutic effects and fewer side effects [64]. When it comesto the different type of processed PC, they have different kindsof effects. For the raw PC, it could downregulate CYP1A2 andactivate CYP3A4. As for rice-wine and salt-water processedPC, they can alter the activities of cytochrome P450. Also,rice-wine processed PC alone can counter the inhibitoryeffect of CYP1A2 and promote the induction of CYP3A4 [65].

6.1. Toxicity and Contraindication. Several studies have beenconducted regarding the toxicology of PC applications. So far,no conclusive result has been reached due to the controversialresults from different studies. The common allegation forPC application is neonatal jaundice and kernicterus. Due tothis concern, it even causes the complete ban on the use ofrelated herbs including PC in Singapore since 1978. Besides,according to the latest Singaporean official regulations for

health supplements guideline, PC is still on the list ofprohibited or restricted ingredients. However, according toa cohort study, under the guidance of Chinese medicinepractitioners, the application of PC’s berberine is clinicallysafe even in patients who have hematological diseases withprofound cytopenia and multiple comorbidities. Despitethese, some precautionary measures such as bilirubin andhemoglobin monitoring are still required for the patientswho have underlining hemolytic disease. On the other hand,the restriction for PC is necessary for the users in theirperipartum and neonatal period due to the concern ofits aggravation risk for neonatal jaundice and kernicterus[66].

6.2. Processing, Differentiation, and Authentication. Tradi-tional Chinese medicine (TCM) processing or preparationor “Pao Zhi” in Chinese is a unique technique and processin TCM. Pao Zhi is a technique to turn the raw herbsinto decoction pieces. This technique must be performedunder the guidance of TCM’s theory to satisfy the differentrequirements of medicinal materials and special productionprocesses. The quality of Pao Zhi directly affects the thera-peutic effects of herbal medicine [67]. It has a time-honoredhistory because as early as 5 B.C. during the Jin dynasty,“Leigong Treatise on the Preparation” was composed as abook for Pao Zhi. It systematically summarized the herbalprocessing techniques until the Jin dynasty. Intriguingly, itstated that the right way of using the bark of PC is toremove the coarse bark [68]. In the Song dynasty, Pao Zhihad regulated a mandatory process for Chinese medicinalproduct [67].

In terms of PC’s processing, TCM doctors in historyemphasized the importance of PC’s processing and recorded16 kinds of methods for PC’s processing in the books. Nowa-days, the most common types of processing are raw PC, PCfried with salt, PC fried with wine, PC fried with honey,and fried-to-charcoal PC [69]. However, it still lacks officialstandard when it comes to quantity and quality of theprocessed PC and its subspecies; some of the existing pioneerstudies could explain this ambiguous and abstract concept ina scientific way. Besides, for PC’s quality control, the mostpractical approach is to use thin layer chromatography (TLC)for qualitative and high-performance liquid chromatography(HPLC) for quantitative measurement [70]. According to theresults of thin layer chromatography, water percentage in theraw PC is less than 10.0%, PC fried with salt is less than 8.0%,PC fried with wine is less than 7.0%, and PC fried with honeyis less than 8.0%. Total ash content in the raw PC is less than8.0%; acid insoluble ash content is less than 0.8%; PC friedwith salt is less than 8.0%; acid insoluble ash content is lessthan 0.6%; PC fried with wine is less than 8.0%; acid insolubleash content is less than 0.8%; PC fried with honey is lessthan 8.0%; acid insoluble ash content is less than 0.4%. Foralcohol-soluble extract, the raw PC is more than 16.0%, PCfried with salt is more than 20.0%, PC fried with wine is morethan 16.0%, and PC fried with honey is more than 22.0%. Forpercentage of phellodendrine, the raw PC ismore than 0.41%,and berberine is more than 3.92%; PC fried with salt is morethan 0.36%, and berberine is more than 3.89%; PC fried with

38 Evidence-Based Complementary and Alternative Medicine

Table6:Ph

armacologicalactiv

ities

ofPC

andprocessedPC

.

PharmacologicalAc

tivity

Teste

dSubstance

Invivo/

Invitro

Mod

elor

sample

Activ

econ

centratio

nAd

ministratio

n(In

vivo)

References

Anti-infl

ammatorye

ffect

PARextractw

ithvoucher

specim

ens

Invitro

BV2cells

(Mou

semicroglialcell

line)

100𝜇

g/ml

[28]

PCCextract

Invivo,in

vitro

12-O

-Tetradecano

ylph

orbo

l-13-

acetate-indu

cedmou

seear

edem

a

(i)TP

AandAAtests

:0.5m

g/ear

(ii)T

PAmultip

leapplication:

1mg/ear

(iii)DTH

test:

1mg/ear

Topicalapp

lication

[29]

PCCextractw

ithvoucher

specim

ens

Invivo,in

vitro

lipop

olysaccharides-in

duced

syste

micinflammationmice

mod

elandmacroph

ageR

AW264.7cells

1,10,100𝜇

g/mL

Oraladm

inistratio

n[30]

Ethano

lextractof

PCCwith

voucherspecimens

Invivo

12-O

-tetradecanoyl-p

horbol-13-

acetate-indu

cedeare

demain

mice

200-40

0mg/kg

Administered

intragastrically

[3]

PARmethano

lextractwith

voucherspecimens

Invitro

,in

vivo

ICRmicea

ndmaleW

istar

rats

IC50:

Methano

lextract20.9±

3.8𝜇

g/mL;

Non

-alkaloids

22.0𝜇g/mL;

Limon

in15.8±5.2𝜇

m;

Obaku

none

2.6±1.1𝜇m

Oraladm

inistratio

n[11]

PCCmethano

lextractwith

voucherspecimens

Invivo

Lipo

polysaccharid

es-ind

uced

acutea

irway

inflammationon

amou

semod

el100,200and40

0mg/kg

Administratedby

gavage

[31]

Dem

ethyleneberberine

Invivo

Acutec

olitism

icem

odel

150,300m

g/kg

Oraladm

inistratio

n[32]

Anti-b

acteria

leffect

Ethano

lExtractof

PAR;

Aqueou

sextractof

PAR

Invitro

Enterococcus

faecium,

Staphylococcus

aureus,

Streptococcusp

yogenes,

Escherichiac

oli,Klebsiella

pneumon

ia,Pseud

omon

asaerugino

sa

MIC

andMBC

:3.676m

g/mland

7.353

mg/mlfor

ethano

lextract;

6.25

mg/mland

50mg/ml

fora

queous

extract

[33]

PCCextractw

ithvoucher

specim

ens

Invitro

Streptococcus.mitis,

Streptococcus.sang

uis,

Streptococcus.mutans,

Streptococcus.ging

ivalis

2.5g

/ml

[34]

PCCextract

Invitro

Mycop

lasm

ahom

inis

0.24-250

mg/ml

[35]

Evidence-Based Complementary and Alternative Medicine 39

Table6:Con

tinued.

PharmacologicalAc

tivity

Teste

dSubstance

Invivo/

Invitro

Mod

elor

sample

Activ

econ

centratio

nAd

ministratio

n(In

vivo)

References

Aqueou

sextractof

PCC

Invivo,

Invitro

S.Ty

phim

urium

21infected

mou

semod

el2.5o

r5mg/day

Administratedby

gavage

[36]

BerberineinPA

RIn

vitro

Staphylococcus

aureus

32to

128𝜇

g/mL

[37]

BerberineinPC

SIn

vitro

P.aerugino

sa100m

l[38]

PCC

Invitro

Prop

ionibacterium

acnes

MIC50%:24𝜇

g/mL

MIC90%:

190𝜇

g/mL

[39]

Anti-fun

galeffect

Berberineh

ydrochlorid

e,palm

atineh

ydrochlorid

eIn

vitro

,In

vivo

Microsporum

Canis–ind

uced

derm

atitisinrabb

itsMIC

s1m

g/ml

Administered

throug

hthes

terile

pipette

tip[40]

Anti-v

iraleffect

Ethano

lextractof

PAR;

Aqueou

sextractof

PAR

Invitro

African

greenmon

keykidn

eycells

6.73±0.87

mg/mlfor

aqueou

sextract;

4.26±0.59

mg/mlfor

ethano

lextract

[33]

Aqueou

sextractof

PARwith

voucherspecimens

Invitro

,in

vivo

H1N

1,H5N

2,H7N

3orH

9N2

infected

BALB

/cmice

0.8𝜇

g/gin

atotalvolumeo

f200𝜇

lat1,3

and5d

ays

before

infection

Oraladm

inistratio

n[41]

Anti-tum

oreffect

PCSextractw

ithvoucher

specim

ens

Invitro

(i)Leuk

emiccelllin

esK5

62(ii)L

eukemiccelllin

esHEL

(iii)Breastcancer

celllin

eMDA

(iv)P

rosta

tecancer

celllin

ePC3

(i)IC50of

Com

poun

d1:

7.66±2.08;

(ii)IC 50of

compo

und3:

14.30±1.9

3;(iii)IC50of

compo

und4:

11.81±2.79

[42]

PCCextract

Invivo,in

vitro

Prostatecancer

cellinfeste

dMale

BALB

/c-nud

emicem

odel

1.6g/kg

perd

ayfor2

8days

Administered

intragastrically

[43]

40 Evidence-Based Complementary and Alternative Medicine

Table6:Con

tinued.

PharmacologicalAc

tivity

Teste

dSubstance

Invivo/

Invitro

Mod

elor

sample

Activ

econ

centratio

nAd

ministratio

n(In

vivo)

References

Aqueou

sextractof

PCSwith

voucherspecimens

Invitro

Invivo

Sarcom

a180

ascitesc

ells

implantedMicem

odel

2mg/100g;

5mg/100g;

10mg/100g

Injected

intraperito

neallydaily

for10days

[44]

Anti-g

outeffect

Com

poun

dsof

Si-M

iao-Wan

(con

tainingPC

C)In

vivo

MaleS

prague-D

awleyr

ats

1.0ml/100

gOraladm

inistratio

n[45]

PCSextractw

ithvoucher

specim

ens

Invivo

Uric

aseinh

ibito

rpotassiu

moxon

ateind

uced

maleICR

mice

mod

el480m

g/kg

Oralorintraperiton

eal

administratio

n[46]

Anti-u

lcereffect

Ethano

lextractof

PCCwith

voucherspecimens

Invivo

Invitro

Aceticacid-in

ducedchronic

gastr

iculcerson

Spragu

eDaw

ley

ratsmod

el30

mg/kg/day

Administered

intragastrically

once

aday

forseven

days.

[47]

Aqueou

sextractof

PCC

Invivo

Ethano

l-ind

uced

gastr

iclesio

nson

MaleW

istar

ratsmod

el100m

g/kg

Oraladm

inistratio

n[48]

Anti-o

xidant

effect

Ethano

lextractof

PAR;

Aqueou

sextractof

PAR

Invitro

Fora

nti-m

icrobialEn

terococcus

faecium,Staph

ylococcusaureus,

Streptococcusp

yogenes,

Escherichiac

oli,Klebsiella

pneumon

ia,and

Pseudo

mon

asaerugino

sa;

Anti-h

erpessim

plex

virustested

onAfrican

greenmon

keykidn

eycells

25mg/ml

[33]

Phellodend

rineisolatedfro

mPC

Cextract

Invivo

AAPH

-indu

cedoxidatives

tress

onzebrafish

embryo

mod

el200𝜇

g/mL

Waterbo

rnee

xposure

[49]

Evidence-Based Complementary and Alternative Medicine 41

Table6:Con

tinued.

PharmacologicalAc

tivity

Teste

dSubstance

Invivo/

Invitro

Mod

elor

sample

Activ

econ

centratio

nAd

ministratio

n(In

vivo)

References

Sunscreeningeffect

PCCextract+

50%ethano

lIn

vitro

PCextract+50%ethano

l0.5m

g/ml

[50]

PCCextract

Invivo

UVBlampinflicted

skin

lesio

nson

thed

orsalofthe

ratsmod

el200,40

0or

800m

g/kg,

once

daily

for11d

ays

Oraladm

inistratio

n[51]

Bone-growth

effect

PCCextract

Invivo

72intact21-day-old

female

Spragu

e–Daw

leyr

ats

100and300m

g/kg

Oraladm

inistratio

n[52]

Hem

ostatic

effect

PCCCarbo

nisatus-carbon

dots

Invivo

Invitro

Mou

setailam

putatio

nandliver

scratchon

maleK

unmingmice

mod

els

5,2and1m

g/kg

Subcutaneous

administratio

n[53]

Neuroprotectiv

eeffect

PCCextractw

ithvoucher

specim

ens

Invitro

PC-12cells

10and30𝜇g/mL

[54]

PCCandPA

Cextractw

ithvoucherspecimens

Invitro

PC-12cells

0.1a

nd1g/m

lfor

2ho

urs

[55]

Cou

nter-atopicd

ermatitis

effect

SaltprocessedPA

Cextractw

ithvoucherspecimens

Invivo

2,4-dinitro

chlorobenzene

indu

cedskin

lesio

nson

the

NC/

Nga

micem

odel

200𝜇

lTo

picaladm

inistratio

n[56]

Cou

nter-diabetic

neph

ropathyeffect

PARaqueou

sextract

Invivo

Streptozotocin-in

duceddiabetes

onmaleS

prague-D

awleyr

ats

mod

el379m

g/kg

Oraladm

inistratio

n[57]

Berberine

Invivo

Streptozotocin-in

duceddiabetes

onmaleW

istar

ratsmod

el200m

g/kg

once

aday

for12

weeks

Oralintub

ation

[58]

Immun

itysupp

ressing

effect

Phellodend

rinea

ndcyclop

hosphamideisolatedfro

mPC

Cin

salin

ewater

Invivo

ddYmice,BA

LB/cmice,and

Hartlaygu

inea

pigs

(i)0.1m

l/10g

form

ice

(ii)1

mlfor

guinea

pigs

Administered

intraperito

neally

[59]

Anti-a

sthmaticeffect

n-bu

tylalcoh

olextracto

fPCS

with

voucherspecimens

Invivo

BALB

/cmicea

sthmaticmod

elindu

cedby

salin

esolution

TheIC5

0of

n-bu

tylalcoh

olextracto

fPCS

was

12.2±

1.3𝜇g/mL

intranasally

[6]

42 Evidence-Based Complementary and Alternative Medicine

honey is more than 0.37%, and berberine is more than 3.90%[69].

Previously, the differentiation of PCS and PAR is basedon the experiences of the herbal professionals to distinguishthe minor differences from their appearances in naked eyesand microscope. Due to the increasing mixing applicationsand counterfeits, more efficient and accurate approaches arerequired. It is noticeable that the mass fractions of obacu-lactone and obacunone have a plunging order among rawPC, PC fried with wine, and PC fried with salt. There-fore, it is reasonable to deduce limonin and obacunonehave been undergoing a series of chemical reactions duringherbal processing. For differentiation of PCS and PAR, themass fractions of limonin and obacunone have a significantdifference between PCS and PAR. The mass fraction ofobaculactone and obacunone in PAR is 10 times higher thanin PCS. As a result, limonin and obacunone could be utilizedas the differential targeted chemical constituents for PC’sdifferentiation [71]. HPLCmethod demonstrates that PC andcharcoaled PC have a significant disparity in terms of charac-teristic chromatograms and chemical constituents. The peaknumbers and proportions of characteristic chromatogramsare reducing with the increasing temperature of charcoaledPC. On the other hand, due to the heating effect, berberinehydrochloride will transfer into berberrubine by losing onemethyl. As a result, berberrubine is vindicated to be anothertargeted chemical constituent for charred PC identification[72]. For authentication of PC and its subspecies, berberinehydrochloride could be used as another targeted chemicalconstituent except for limonin and obacunone as mentionedabove [73].

7. Discussion

This review work has illustrated the diverse bioactive proper-ties of PC and its species associated with active pharmacolog-ical actions in vitro and in vivo. Its clinical applications whichare demonstrated in these experimental studies indicated thepotency of the bioactive compounds and its pharmacologicaleffects.

The diverse derivatives are the backbone for the phar-maceutical efficacies of PC and its species. The alkaloidsplay a very significant role in this regard not only becausethey account for a great proportion of constituents in thewhole herb, but also because these constituents are relativelywell-studied compared to other constituents in other deriva-tives. Berberine, magnoflorine, palmatine, and phelloden-drine are viewed as the anti-inflammatory active candidatesin experimental studies. Besides, palmatine and berberinecould exert antimicrobial effects. Berberine also has theability to inhibit monoamine oxidase-A and modulate thebrain noradrenaline, serotonin, and dopamine for antiulcerefficacy. The nonalkaloid in PAR extract suppressed NOproduction; besides, limonin and obakunone significantlydownregulatedNOproduction and iNOS gene expression viaan NF-𝜅B-mediated pathway. [(21S, 23R) Epoxy-24-hydroxy-21𝛽, 25-diethoxy] tirucalla-7-en-3-one, toonaciliatin K, andpiscidinol have tumor-shrinking effects on four types oftumors. Polysaccharides from an aqueous extract of PCS act

on cell-mediated stimulation and humoral immunity to exerttumoricidal activity.

Phellodendrine and magnoflorine have well absorptionrate in the animal organs which could indicate their safety forhuman trials. However, berberine could interact with mag-noflorine or other constituents which could further increasethe tissue absorption rates. This should be noticed by otherclinical trials or advanced studies to avoid adverse effects. Itis also noticeable that different processing techniques or “PaoZhi” could render the herb with different kind of therapeuticeffects. For the raw PC, it could downregulate CYP1A2 andactivate CYP3 A4. As for rice-wine and salt-water processedPC, they can alter the activities of cytochrome P450. Also, forrice-wine processed PC alone, it can counter the inhibitoryeffect of CYP1A2 and promote the induction of CYP3A4. Fortoxicology, there is no affirmative conclusion in terms of PCand its species’ absolute clinical safety. Therefore, safety pre-cautionary measures are still required for vulnerable groupsof people. For the processed PC and its species, berber-rubine, limonin, and obacunone became targeted chemicalconstituents for authentication of charred PC, PC, and itssubspecies. Furthermore, obacunone and obaculactone areprobably responsible for antiatopic dermatitis effect [56].

8. Conclusions

In summary, the compounds of the crude bark of PC andits species have showcased a wide range of pharmacologicaleffects. Pharmacological efficacies of PC are supported by itsdiverse class of alkaloids, limonoids, phenolic acid, quinicacid, lignans, and flavonoid. Through this review, in total, 140chemical compounds had been summarized. Among thesecompounds are 18 compounds from PCC, 44 compoundsfrom PCS, 34 compounds from PAC, and 84 compoundsfrom PAR. However, more studies are still needed to demon-strate more knowledge to allow a better understanding of thisherb and its species.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

[1] Y. Q. Dong, H. X. Hong, and G. Y. Zhong, “Research status andproblems of phellodendron quality,” Research and Practice ofChinese Medicines, vol. 3, 2007.

[2] Y. Zheng, R. H. Hui, and D. Y. Hou, “Studies on flavonesand anti-oxidation effect of phellodendron,” Journal of AnshanNormal University, 2010.

[3] Y.-F. Xian, Q.-Q. Mao, S.-P. Ip, Z.-X. Lin, and C.-T. Che,“Comparison on the anti-inflammatory effect of Cortex Phel-lodendri Chinensis and Cortex Phellodendri Amurensis in12-O-tetradecanoyl-phorbol-13-acetate-induced ear edema inmice,” Journal of Ethnopharmacology, vol. 137, no. 3, pp. 1425–1430, 2011.

[4] X. Li, W. Zhang, H. Qi, and Y. Shi, “Phenolic constituents ofPhellodendron chinense bark,” Canadian Journal of Chemistry,vol. 87, no. 9, pp. 1218–1221, 2009.

Evidence-Based Complementary and Alternative Medicine 43

[5] J. A. Ryuk, M. S. Zheng, M. Y. Lee et al., “Discriminationof Phellodendron amurense and P. chinense based on DNAanalysis and the simultaneous analysis of alkaloids,” Archives ofPharmacal Research, vol. 35, no. 6, pp. 1045–1054, 2012.

[6] Q.-J. Jiang,W. Chen, H. Dan et al., “Cortex phellodendri extractrelaxes airway smoothmuscle,”Evidence-Based Complementaryand Alternative Medicine, vol. 2016, Article ID 8703239, 9 pages,2016.

[7] X. Cao, L. Sun, D. Li, G. You, M. Wang, and X. Ren, “Qualityevaluation of phellodendri chinensis cortex by fingerprintchemical pattern recognition,” Molecules, vol. 23, no. 9, article2307, 2018.

[8] H. Wang, G. Yan, A. Zhang et al., “Rapid discovery and globalcharacterization of chemical constituents and rats metabolitesof Phellodendri amurensis cortex by ultra-performance liquidchromatography-electrospray ionization/quadrupole-time-of-flight mass spectrometry coupled with pattern recognitionapproach,” Analyst, vol. 138, no. 11, p. 3303, 2013.

[9] Y. M. Hu, G. H. Su, S. C.-W. Sze, W. Ye, and Y. Tong, “Qualityassessment of Cortex phellodendri by high-performance liquidchromatography coupled with electrospray ionization massspectrometry,” Biomedical Chromatography, vol. 24, no. 4, pp.438–453, 2010.

[10] H. Sun, H. Wang, A. Zhang et al., “Chemical discriminationof cortex Phellodendri amurensis and cortex Phellodendrichinensis by multivariate analysis approach,” PharmacognosyMagazine, vol. 12, no. 45, pp. 41–49, 2016.

[11] A. Fujii, T. Okuyama, K. Wakame, T. Okumura, Y. Ikeya, andM.Nishizawa, “Identification of anti-inflammatory constituentsin Phellodendri Cortex and Coptidis Rhizoma by monitoringthe suppression of nitric oxide production,” Journal of NaturalMedicines, vol. 71, no. 4, pp. 745–756, 2017.

[12] Z. Zhang, H. Liu, B. Zhang, Y. Liao, Y. Zhang, and Z. Zhang,“Quantitative and chemical fingerprint analysis for qualityevaluation of the dried bark of wild Phellodendron amurenseRupr. based on HPLC-DAD-MS combined with chemometricsmethods,” Analytical Methods, vol. 7, no. 5, pp. 2041–2049, 2015.

[13] J. Zhou, G. Xie, and X. Yan, Encyclopedia of Traditional ChineseMedicines - Molecular Structures, Pharmacological Activities,vol. 1, Isolated Compounds A-C, 1st edition, 2011.

[14] X. Li, J. Liang, X. Lu, and L. Tao, “A new protoberberine fromthe bark of Phellodendron chinense,” Chemistry of NaturalCompounds, vol. 47, no. 5, pp. 770–772, 2011.

[15] X. Xian, B. Sun, X. Ye, G. Zhang, P.Hou, andH.Gao, “Identifica-tion and analysis of alkaloids in cortex Phellodendron amurenseby high-performance liquid chromatography with electrosprayionization mass spectrometry coupled with photodiode arraydetection,” Journal of Separation Science, vol. 37, no. 13, pp. 1533–1545, 2014.

[16] Y.-M. Liu, S.-J. Sheu, S.-H. Chiou, H.-C. Chang, and Y.-P. Chen,“A comparative study on commercial samples of Phellodendricortex,” Planta Medica, vol. 59, no. 6, pp. 557–561, 1993.

[17] J. Zhou, G. Xie, and X. Yan, “Encyclopedia of TraditionalChinese Medicines - Molecular Structures, PharmacologicalActivities, Natural Sources and Applications,” Isolated Com-pounds D-G, vol. 2, 2011.

[18] J. Zhou, G. Xie, and X. Yan, Encyclopedia of Traditional ChineseMedicines - Molecular Structures, Pharmacological Activities,Natural Sources and Applications, vol. 4, Isolated CompoundsN-S, 1st edition, 2011.

[19] J. Zhou, G. Xie, and X. Yan, Encyclopedia of Traditional ChineseMedicines - Molecular Structures, Pharmacological Activities,

Natural Sources and Applications, vol. 3, Isolated CompoundsH-M, 1st edition, 2011.

[20] Y. D. Min, H. C. Kwon, M. C. Yang et al., “Isolation oflimonoids and alkaloids from Phellodendron amurense andtheir multidrug resistance (MDR) reversal activity,” Archives ofPharmacal Research, vol. 30, no. 1, pp. 58–63, 2007.

[21] C. D. Li, Y. Liu, and Y. P. Shi, “Simultaneous determination ofsix alkaloids in Phellodendron amurense by high-performanceliquid chromatography,” Acta Chromatographica, vol. 25, no. 2,pp. 275–285, 2013.

[22] Y. P. Li, D. D. Li, L. Q. Ding, and F. Qiu, “Non-alkoloidscomponents from Phellodendri Cortex,” Chinese Traditionaland Herbal Drugs, vol. 47, no. 15, pp. 2621–2626, 2016.

[23] Z. Zhang, Y. Zhang, Z. Zhang et al., “Comparative analysis ofDNA barcoding and HPLC Fingerprint to trace species of phel-lodendri cortex, an Important Traditional Chinese Medicinefrom multiple sources,” Biological & Pharmaceutical Bulletin,vol. 39, no. 8, pp. 1325–1330, 2016.

[24] Y. Ida, Y. Satoh,M.Ohtsuka,M.Nagasao, and J. Shoji, “Phenolicconstituents of phellodendron amurense bark,” Phytochemistry,vol. 35, no. 1, pp. 209–215, 1993.

[25] H. Zhou, D. Wang, and Z. Cui, “Ferulates, amurenlactone Aand amurenamide A from traditional Chinese medicine cortexPhellodendri Amurensis,” Journal of Asian Natural ProductsResearch, vol. 10, no. 5, pp. 409–413, 2008.

[26] O. I. Shevchuk, N. P. Maksyutina, and V. I. Litvinenko,“Flavonoids of Phellodendron sachalinense and Ph. amurense,”Chemistry of Natural Compounds, vol. 4, no. 2, pp. 66–70, 1968.

[27] W. Cui, J. Tian, Z. Ma, Y. Guo, J. Wang, and X. Li, “A newisocoumarin from bark of Pellodendoron chinense,” NaturalProduct Research, vol. 17, no. 6, pp. 427–429, 2003.

[28] Y.-k. Park, Y. S. Chung, Y. S. Kim, O. Y. Kwon, and T. H.Joh, “Inhibition of gene expression and production of iNOSand TNF-𝛼 in LPS-stimulated microglia by methanol extract ofPhellodendri cortex,” International Immunopharmacology, vol.7, no. 7, pp. 955–962, 2007.

[29] M. J. Cuellar, R. M. Giner, M. C. Recio, S. Manez, and J. L. Rios,“Topical anti-inflammatory activity of some Asian medicinalplants used in dermatological disorders,” Fitoterapia, vol. 72, no.3, pp. 221–229, 2001.

[30] Y. Y. Choi, M. H. Kim, J. M. Han et al., “The anti-inflammatorypotential of cortex phellodendron in vivo and in vitro: down-regulation of NO and iNOS through suppression of NF-𝜅B andMAPK activation,” International Immunopharmacology, vol. 19,no. 2, pp. 214–220, 2014.

[31] Y.-F. Mao, Y.-Q. Li, L. Zong, X.-M. You, F.-Q. Lin, and L.Jiang, “Methanol extract of Phellodendri cortex alleviateslipopolysaccharide-induced acute airway inflammation inmice,” Immunopharmacology and Immunotoxicology, vol. 32,no. 1, pp. 110–115, 2010.

[32] Y. Chen, R. Li, M. Shi et al., “Demethyleneberberine alleviatesinflammatory bowel disease in mice through regulating NF-𝜅B signaling and T-helper cell homeostasis,” InflammationResearch, vol. 66, no. 2, pp. 187–196, 2017.

[33] W.Wang, Y. Zu, Y. Fu et al., “In vitro antioxidant, antimicrobialand anti-herpes simplex virus type 1 activity of Phellodendronamurense Rupr,” American Journal of Chinese Medicine, vol. 37,no. 1, pp. 195–203, 2009.

[34] R. W. K. Wong, U. Hagg, L. Samaranayake, M. K. Z. Yuen, C.J. Seneviratne, and R. Kao, “Antimicrobial activity of Chinesemedicine herbs against commonbacteria in oral biofilm.A pilot

44 Evidence-Based Complementary and Alternative Medicine

study,” International Journal of Oral and Maxillofacial Surgery,vol. 39, no. 6, pp. 599–605, 2010.

[35] Y. Che, S. Mao,W. Jiao, and Z. Fu, “Susceptibilities ofMycoplas-ma hominis to herbs,” American Journal of Chinese Medicine,vol. 33, no. 2, pp. 191–196, 2005.

[36] M. C. Yin, C. H. Chang, C. H. Su, B. Yu, and Y. M. Hsu, “Pterismultifida, Cortex phellodendri, and probiotics attenuatedinflammatory status and immunity in mice with a Salmonellaenterica serovar Typhimurium infection,” Bioscience, Biotech-nology, and Biochemistry, pp. 1–12, 2018.

[37] H.-H. Yu, K.-J. Kim, J.-D. Cha et al., “Antimicrobial activity ofberberine alone and in combination with ampicillin or oxacillinagainst methicillin-resistant Staphylococcus aureus,” Journal ofMedicinal Food, vol. 8, no. 4, pp. 454–461, 2005.

[38] Y. Morita, K. Nakashima, K. Nishino et al., “Berberine is a noveltype efflux inhibitor which attenuates the MexXY-mediatedaminoglycoside resistance in Pseudomonas aeruginosa,” Fron-tiers in Microbiology, vol. 7, article 1223, 2016.

[39] S. Higaki, M. Nakamura, M. Morohashi, Y. Hasegawa, and T.Yamagishi, “Activity of eleven Kampo formulations and eightKampo crude drugs against Propionibacterium acnes isolatedfrom acne patients: retrospective evaluation in 1990 and 1995,” e Journal of Dermatology, vol. 23, no. 12, pp. 871–875, 1996.

[40] C. Xiao, Q. Ji, Q. Wei, Y. Liu, and G. Bao, “Antifungal activ-ity of berberine hydrochloride and palmatine hydrochlorideagainst Microsporum canis -induced dermatitis in rabbits andunderlying mechanism,” BMC Complementary and AlternativeMedicine, vol. 15, article 177, 2015.

[41] J. Kim, P. Weeratunga, M. S. Kim et al., “Inhibitory effects of anaqueous extract from Cortex Phellodendri on the growth andreplication of broad-spectrum of viruses in vitro and in vivo,”BMC Complementary and Alternative Medicine, vol. 16, article265, 2016.

[42] C. Yan, Y.-D. Zhang, X.-H.Wang et al., “Tirucallane-type triter-penoids from the fruits of Phellodendron chinense Schneid andtheir cytotoxic activities,” Fitoterapia, vol. 113, pp. 132–138, 2016.

[43] X. Li, A. Zhang, M. Wang et al., “Screening the active com-pounds of Phellodendri Amurensis cortex for treating prostatecancer by high-throughput chinmedomics,” Scientific Reports,vol. 7, article 46234, 2017.

[44] S.-D. Park, Y.-S. Lai, and C.-H. Kim, “Immunopontentiatingand antitumor activities of the purified polysaccharides fromPhellodendron chinese SCHNEID,” Life Sciences, vol. 75, no. 25,pp. 2621–2632, 2004.

[45] J.-J. Lu, X.-W. Hu, P. Li, and J. Chen, “Global identificationof chemical constituents and rat metabolites of Si-Miao-Wanby liquid chromatography-electrospray ionization/quadrupoletime-of-flight mass spectrometry,” Chinese Journal of NaturalMedicines, vol. 15, no. 7, pp. 550–560, 2017.

[46] L. D. Kong, C. Yang, F. Ge, H. D. Wang, and Y. S. Guo, “AChinese herbal medicine Ermiao wan reduces serum uric acidlevel and inhibits liver xanthine dehydrogenase and xanthineoxidase inmice,” Journal of Ethnopharmacology, vol. 93, no. 2-3,pp. 325–330, 2004.

[47] L. Wang, X. Wang, X. Zhu et al., “Gastroprotective effect ofalkaloids from cortex phellodendri on gastric ulcers in ratsthrough neurohumoral regulation,” Planta Medica, vol. 83, no.3-4, pp. 277–284, 2017.

[48] H. Takase, O. Inoue, Y. Saito, E. Yumioka, and A. Suzuki, “Rolesof sulfhydryl compounds in the gastric mucosal protection ofthe herb drugs composing oren-gedoku-to (a traditional herbal

medicine),” e Japanese Journal of Pharmacology, vol. 56, no.4, pp. 433–439, 1991.

[49] L. Li, T. Huang, C. Tian et al., “The defensive effect of phel-lodendrine against AAPH-induced oxidative stress throughregulating the AKT/NF-𝜅B pathway in zebrafish embryos,” LifeSciences, vol. 157, pp. 97–106, 2016.

[50] S. Y. Cheng, D. X. Luo, Q. J. He, and Z. H. Li, Determinationof the Sun-screening Effect for 50% Alcohol Extracts of 100Chinese Herbal Medicine Most in Use, China Academic JournalElectronic Publishing House, 2005.

[51] H. Yan, X. Sun, S. Sun et al., “Anti-ultraviolet radiation effectsof Coptis chinensis and Phellodendron amurense glycans byimmunomodulating and inhibiting oxidative injury,” Interna-tional Journal of Biological Macromolecules, vol. 48, no. 5, pp.720–725, 2011.

[52] S. H. Lee, H. J. Lee, S. H. Lee et al., “Effects of Huang Bai (Phel-lodendri Cortex) on bone growth and pubertal development inadolescent female rats,” Chinese Medicine, vol. 13, no. 3, 2018.

[53] X. Liu, Y. Wang, X. Yan et al., “Novel Phellodendri Cortex(Huang Bo)-derived carbon dots and their hemostatic effect,”Nanomedicine, vol. 13, no. 4, pp. 391–405, 2018.

[54] H. W. Jung, G.-Z. Jin, S. Y. Kim, Y. S. Kim, and Y.-K. Park,“Neuroprotective effect of methanol extract of PhellodendriCortex against 1-methyl-4-phenylpyridinium (MPP+)-inducedapoptosis in PC-12 cells,” Cell Biology International, vol. 33, no.9, pp. 957–963, 2009.

[55] Y.-F. Xian, Z.-X. Lin, S.-P. Ip, Z.-R. Su, J.-N. Chen, and X.-P. Lai,“Comparison the neuropreotective effect of Cortex Phelloden-dri chinensis and Cortex Phellodendri amurensis against beta-amyloid-induced neurotoxicity in PC12 cells,” Phytomedicine,vol. 20, no. 2, pp. 187–193, 2013.

[56] S. Park, D. S. Kim, S. Kang, and B. K. Shin, “Synergistictopical application of salt-processed Phellodendron amurenseand Sanguisorba officinalis Linne alleviates atopic dermatitissymptoms by reducing levels of immunoglobulin E and pro-inflammatory cytokines in NC/Nga mice,” Molecular MedicineReports, vol. 12, no. 5, pp. 7657–7664, 2015.

[57] H.-J. Kim, M.-K. Kong, and Y.-C. Kim, “Beneficial effects ofPhellodendri Cortex extract on hyperglycemia and diabeticnephropathy in streptozotocin-induced diabetic rats,” Journal ofBiochemistry and Molecular Biology, vol. 41, no. 10, pp. 710–715,2008.

[58] W. Liu, P. Liu, S. Tao et al., “Berberine inhibits aldose reductaseand oxidative stress in rat mesangial cells cultured under highglucose,”Archives of Biochemistry and Biophysics, vol. 475, no. 2,pp. 128–134, 2008.

[59] H. Mori, M. Fuchigami, N. Inoue, H. Nagai, A. Koda, and I.Nishioka, “Principle of the bark of Phellodendron amurense tosuppress the cellular immune response,” PlantaMedica, vol. 60,no. 5, pp. 445–449, 1994.

[60] J. Kreiner, E. Pang, G. B. Lenon, and A. W. Yang, “Saposh-nikoviae divaricata: a phytochemical, pharmacological, andpharmacokinetic review,”Chinese Journal of Natural Medicines,vol. 15, no. 4, pp. 255–264, 2017.

[61] S. A. Heleno, A. Martins, M. J. Queiroz, and I. C. Ferreira,“Bioactivity of phenolic acids: metabolites versus parent com-pounds: a review,” Food Chemistry, vol. 173, pp. 501–513, 2015.

[62] H. Q. Shan, L. S. Duan, X. Qi, and W. Yang, “Quality con-trol of preparations with phellodendron chinense schneid orphellodendron amurense rupr in three editions of Chinesepharmacopoeia,” Chinese Pharmaceutical Affairs, 2016.

Evidence-Based Complementary and Alternative Medicine 45

[63] Y. Li, X. Liu, H. Wang et al., “Pharmacokinetic studiesof phellodendrine in rat plasma and tissues after intra-venous administration using ultra-high performance liquidchromatography–tandem mass spectrometry,” Journal of Chro-matography B, vol. 1029-1030, pp. 95–101, 2016.

[64] X. Tian, Z. Li, Y. Lin, M. Chen, G. Pan, and C.Huang, “Study onthe PK profiles of magnoflorine and its potential interaction inCortex phellodendri decoction by LC-MS/MS,” Analytical andBioanalytical Chemistry, vol. 406, no. 3, pp. 841–849, 2014.

[65] P.-P. Liu, T.-Z. Jia, S. Xu, and F. Zhang, “Application of cocktailprobe drugs for detecting influences of raw and processedphellodendri cortex on cytochrome P450 isoforms,” Journal ofChineseMedicinalMaterials, vol. 38, no. 10, pp. 2065–2069, 2015.

[66] Y.-C. Linn, J. Lu, L.-C. Lim et al., “Berberine-induced haemoly-sis revisited: safety of Rhizoma coptidis and Cortex phelloden-dri in chronic haematological diseases,” Phytotherapy Research,vol. 26, no. 5, pp. 682–686, 2012.

[67] H.W. Yao andY. Liu, “Study of the processing of Chinese herbalmedicine: status quo and development strategy,” China Pharm,2008.

[68] M. Jin, “Discussion on the easily confusing species HuangBai and Guan Huangbai in the adjustment,” in Capital FoodMedicine, 2018.

[69] Q. Wu, C. G. Ju, X. Ai, and F. Zhang, “Study on the qualitystandards of cork and its different processed products fromdifferent places of purchase,” Asia-Pacific Traditional Medicine,2017.

[70] S. Zhou, Y. G. Liu, G. X. Zhang, and Z. L. Chen, ResearchProgress on Chemical Composition and Quality Control ofCorktree, China Pharm, 2012.

[71] Z. L. Zhang,D.H. Liu, Y. C.Huang, andG.Wei, “Determinationof limonin and obacunone in Phellodendri Amurensis Cortex,Phellodendri Chinensis Cortex and their processed products byHPLC,” Chinese Traditional Patent Medicine, 2011.

[72] H. Su, L. Yue, Y. Liu et al., “Comparison on HPLC specificchromatograms between phellodendri Chinensis cortex andcharred phellodendri Chinensis cortex decoction pieces,” Chi-nese Journal of Experimental TraditionalMedical Formulae, 2017.

[73] F. L. Liang, H. Z. Zhao, Y. C. Lian, and Z. G. Huang, “Rapiddistinguishment and identification of cortex phellodendri chi-nense and cortex phellodendri amurensis based on TLC,”Journal of Zhaoqing University, 2017.

Stem Cells International

Hindawiwww.hindawi.com Volume 2018

Hindawiwww.hindawi.com Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwww.hindawi.com Volume 2018

Hindawiwww.hindawi.com Volume 2018

Disease Markers

Hindawiwww.hindawi.com Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwww.hindawi.com Volume 2013

Hindawiwww.hindawi.com Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwww.hindawi.com Volume 2018

PPAR Research

Hindawi Publishing Corporation http://www.hindawi.com Volume 2013Hindawiwww.hindawi.com

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwww.hindawi.com Volume 2018

Journal of

ObesityJournal of

Hindawiwww.hindawi.com Volume 2018

Hindawiwww.hindawi.com Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwww.hindawi.com Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwww.hindawi.com Volume 2018

Diabetes ResearchJournal of

Hindawiwww.hindawi.com Volume 2018

Hindawiwww.hindawi.com Volume 2018

Research and TreatmentAIDS

Hindawiwww.hindawi.com Volume 2018

Gastroenterology Research and Practice

Hindawiwww.hindawi.com Volume 2018

Parkinson’s Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwww.hindawi.com

Submit your manuscripts atwww.hindawi.com