Antihyperglycemic, antioxidant and anti-inflammatory effects of umbelliferone in high-fat diet/streptozotocin-induced type 2 diabetic rats

517Thammasat Medical Journal, Vol. 14 No. 4, October – December 2014

Original Articles

Antihyperglycemic, antioxidant and anti-inflammatory effects of umbelliferone in high-fat diet/streptozotocin-induced

type 2 diabetic ratsJarinyaporn Naowaboot*, Nuntiya Somparn*,

Abstract

Introduction: Oxidativestressandchronicinflammationareimportantpathologicalprocessesthatcancauseinsulin

resistanceandtype2diabetesmellitus,andeventuallycomplicationsofdiabetesmellitus.Forthisstudy,

weaimedtoinvestigatetheeffectofumbelliferone(UMB)intheregulationofbloodglucose,hyperlipidemia,

oxidativestress,andchronicinflammationinhigh-fatdiet/streptozotocin-inducedtype2diabeticrats.

Method: MaleWistarratswerefedon45kcal%fatdietfor3weeksfollowedbyintraperitoneallyinjectedwitha

singledoseofstreptozotocin(35mg/kg).DiabeticratswerefedwithUMBfor6weeks.Thefasting

bloodglucose(FBG),lipidprofiles,malondialdehyde(MDA),andinflammatorycytokine;tumornecrosis

factor-α(TNF-α)andmonocytechemoattractantprotein-1(MCP-1)weredetermined.

Result: Type2diabeticratmodelshowedelevatedbloodglucose,impairedglucosetolerance,increasedtotal

cholesterol,triglycerideandnon-esterifiedfattyacid,increasedMDA,andincreasedTNF-αandMCP-1.

TheresultsofthepresentstudyhavebeenshownthattheUMBtreatmentreducedbloodglucoselevel,

improvedglucosetolerance,anddecreasedthelevelsofalloflipidprofiles.Inaddition,serumandtissues

MDAaswellaslevelsofTNF-αandMCP-1inserumweredecreased.

Discussion TheseresultssuggestabeneficialeffectofUMBinreducingthebloodglucose,hyperlipidemia,oxidative

and Conclusion: stressandinflammatorymediatorsintype2diabeticrats.

Key words:Umbelliferone,Type2diabeticrat,Oxidativestress,Inflammation

Received: 21 April 2014 Accepted: 25 August 2014

* DivisionofPharmacology,DepartmentofPreclinicalScience,FacultyofMedicine,ThammasatUniversity,PathumThani12120,Thailand** DivisionofAnatomy,DepartmentofPreclinicalScience,FacultyofMedicine,ThammasatUniversity,PathumThani12120,Thailand*** DepartmentofPharmacology,FacultyofMedicine,KhonKaenUniversity,KhonKaen40002,ThailandCorresponding Author:JarinyapornNaowabootDivisionofPharmacology,DepartmentofPreclinicalScience,FacultyofMedicine,ThammasatUniversity,PathumThani12120,Thailande-mail:[email protected]

Suphaket Saentaweesuk**, Patchareewan Pannangpetch***

518 ธรรมศาสตร์เวชสาร ปีที่ ๑๔ ฉบับที่ ๔ ประจำาเดือนตุลาคม – ธันวาคม ๒๕๕๗

Introduction Type2diabetesmellitus(T2DM)isoneofthe

world’smostcommonchronicdiseasesaschanging

lifestylesleadtoreducedphysicalactivityandincreased

obesity1.EarlyphenomenonofT2DMisinsulininsensitivity,

whichnotonlyhasnegativemetabolicconsequencesbut

alsocontributessubsequentpancreasβ-cellexhaustion,

resultingintheonsetofclinicalhyperglycemia2.

Oxidativestressresultingfromincreasedproduc-

tionofreactiveoxygenspecies(ROS)haveakeyfunction

inthepathogenesisoflatediabeticcomplications3.ROS

resultingfromhyperglycemiaarethoughttocontributeto

theinitiationoflipidperoxidation4.Malondialdehyde(MDA)

isanendproductoflipidperoxidation.Therehasbeena

reportthathyperglycemiaassociatedwithhyperlipidemia

couldbethecausativefactorfortheincreasedproduc-

tionoffreeradicalsandlipidperoxides,thatis,MDA5.

Moreover,hyperglycemiahasbeenshowntoinducethe

expressionofproinflammatorycytokinesandchemokine

genesinmonocyticcells6.Certaininflammatorycytokines,

suchastumornecrosisfactor-α(TNF-α),impairinsulin

actioninperipheraltissueandhaveadirectfunctionin

obesity-associatedinsulinresistance7.

Monocytechemoattractantprotein(MCP)-1isa

C-Cchemokinefamilywithapotentchemotacticfactorfor

monocytes.MCP-1biosynthesisisinducedbyinflammatory

cytokines,oroxidativelymodifiedlowdensitylipoprotein

(LDL)inmonocytes,endothelialcells,andvascularsmooth

musclecells8.Ithasbeendemonstratedthathighglucose

concentrationstimulatestheexpressionofMCP-19 and

theformationofROS10.Aswellas,theantidiabeticdrug,

pioglitazone,causesdecreasedgeneexpressionofMCP-1

inadiposetissue,alongwithanimprovementininsulin

resistance11.

Manykindsofplantsandtheirbioactive

compoundshavebeenshowntoimprovemetabolicabnor-

malities,suchasinsulinresistance,obesity,anddiabetes

mellitus12-13.Coumarinsconstituteaverylargeclassof

compoundspresentinseveralspeciesbelongingtodiffer-

entbotanicalfamilies.Coumarinanditsderivativeshave

beenfoundtohaveawiderangeofbioactivities,such

asantifungal14,antitumor15,antithrombotic,vasodilatory16,

anti-inflammatory,andantioxidantactivities17.Umbellifer-

one(UMB)or7-hydroxycoumarinisawidespreadnatural

productofthecoumarinfamilywithanti-inflammatory

activity18.RecentstudieshaveshownthatUMBcanact

asapotentantioxidativeandantihyperglycemicagentin

streptozotocin-inducedtype1diabeticrats19-20.However,

theanti-inflammationactivityofUMBinhyperglycemicwith

oxidativestressconditionintype2diabeticanimalmodelis

stillnotcompletelyinvestigated.Alsoasmentionedabove

theincidenceoftype2diabetesisincreasing,therefore,

thisstudywasaimedtodeterminetheseeffectsinT2DM

inducedbyhigh-fatdietwithlowdoseofstreptozotocin

(STZ).

MethodChemicals and reagents

Umbelliferoneandallfinechemicalswereobtained

fromSigma-Aldrich(St.Louise,MO,USA).Pioglitazonewas

purchasedfromBerlinPharmaceuticalIndustryCo.,Ltd.

(Latkrabang,Bangkok,Thailand).

Animals and induction of diabetes

Animalexperimentswereperformedaccording

totheanimalcareguidelinesandwereapprovedbythe

AnimalEthicsCommitteeofThammasatUniversity,Pathum

Thani,Thailand(Rec.No.AE008/2013).MaleWistarrats

weighting120-150gwereobtainedfromtheNational

LaboratoryAnimalCenterofMahidolUniversity,Nakhon

Pathom,Thailand.Twoanimalswerehousedpercagein

aroomwitha12/12-hourlight/darkcycleandanambient

temperatureof22to25°C.Theywerefedwithstandard

normaldiet(SND)orHFDcontaining45kcal%fat(soy-

beanoilandlardthatincluded0.95mgcholesterolperg

oflard),35kcal%carbohydratesand20kcal%protein

(Researchdiets,Brunswick,NJ,USA)ad libitumduring3

weeks.After3weeksoftheHFD,ratswerefastedfor

12hours(freeaccesstowater)andwereinjectedwith

asinglelowdoseofSTZ(35mg/kgintraperitoneally).

Ratswereallowedtodevelopdiabetesforaweek.After

that,fastingbloodglucose(FBG)levelsweredetermined


fromtailveinbloodusingglucometer(Accu-Check,Roche

Diagnostics,Manheim,Germany).TheratswithFBGabove

126mg/dL21wereconsidereddiabeticandincludedinthe

experiments.

Experimental design

Theratsweredividedintosixgroupswithsix

ratsineachgroupandtreatedasfollows:group1:normal

controlrats(SNDfeeding)with5%GumArabic;group2:

diabeticcontrolratswith5%GumArabic;group3:diabetic

positivecontrolratswithpioglitazone10mg/kgperday;

group4to6:diabeticratswithUMB10,30,and60mg/

kgperday,respectively20,22.PioglitazoneandUMBwere

suspendedin5%GumArabic.Alltreatmentsweredaily

administratedorallyusingfeedingtubefor6weeks.The

FBGlevelofallratswasmeasuredafter6weeksoftreat-

ment.After6weeksofUMBtreatment,ratswerefasted

overnightandanesthetizedwithether.Theheart,liver,

kidneyandthoracicaortawererapidlyexcisedtoperform

biochemicalexaminationsasdescribedbelowindetail.

Duringfasting,ratsweredeprivedoffoodfor12hoursbut

hadfreeaccessofwater.

Oral glucose tolerance test (OGTT)

After5weeksoftreatment,anOGTTwas

performedtoevaluatetheeffectofeachtreatmenton

glucosetolerance.After12hoursoffasting,ratswere

orallyloadedwithglucose(1.0g/kgofbodyweight)and

bloodglucoselevelsweredeterminedfromthetailvein

bloodbeforeandafterglucoseloadingat30,60,and120

min.Theareaunderthecurve(AUC)ofbloodglucosewas

calculatedfromthebloodconcentration-timerelationships.

Determination of serum lipid profiles

After6weeksofUMBtreatment,serumtriglyc-

eride,totalcholesterolandnon-esterifiedfattyacid(NEFA)

levelsweredeterminedusingenzymaticcolorimetric

method(Wako,Osaka,Japan).

Determination of MDA in liver, kidney, heart and thoracic

aorta

Thetissues(heart,liver,kidneyandthoracicaorta)

werefinelyslicedandhomogenizedincoldphosphate

bufferedsalinewithmagnesiumchloride(pH7.4).After10

minutescentrifugation(14,000 × g,4ºC),theclearsuper-

natantwascollectedforMDAassay.MDAwasexamined

usingTBARSparameterassaykit(R&DSystems,Minne-

apolis,MN,USA).TheMDAconcentrationinthetissues

wasnormalizedagainsttheproteinconcentration.Protein

wasdeterminedbytheBradford’smethod23.

Determination of serum TNF-α and MCP-1 secretion

After6weeksofUMBtreatment,serumTNF-α

andMCP-1concentrationswereassayedusingratTNF-α

ELISAkit(R&DSystems,Minneapolis,MN,USA)andrat

MCP-1ELISAkit(ThermoScientific,Rockford,IL,USA).

Statistical analyses

Resultswereexpressedasthemeanvalueswith

theirstandarderrorsofeachgroup.Multiplecomparisons

wereanalyzedbyanalysisofvariance(ANOVA)andTukey’s

post-hoctest.Thestatisticalanalyseswereperformedus-

ingcomputer-basedsoftwareSigmaStat(SystatSoftware,

CA,USA).Thelevelofsignificancewasuniformlysetat

p<0.05.

ResultEffect of UMB on fasting blood glucose

Afteraperiodof6weeks,theFBGlevelofthe

diabeticcontrolgroupwasstillhigh.However,alldoses

ofUMB(10,30,and60mg/kg)significantlyreducedblood

glucoselevels(35%,44%,and29%respectively;p<0.05)

(Figure1A).Anoraladministrationofpositivecontrol10

mg/kgpioglitazonereducedbloodglucoselevelsofdiabetic

ratsby46%(Figure1A).


Figure 1EffectofUMBonfastingbloodglucose(A),OGTT(B)andAUCinOGTT(C)inhigh-fatdiet/streptozotocin-induced

type2diabeticrats.Valuesweremean±S.E.M.(n =6).*p<0.05whencomparedtonormalcontrolgroup;#p<0.05

whencomparedtodiabeticcontrolgroup.NR:normalcontrolrattreatedwith5%GumArabic;DM:diabetic

controlrattreatedwith5%GumArabic;DM+Pio:diabeticrattreatedwithpioglitazone10mg/kg;DM+UMB:

diabeticrattreatedwithumbelliferone10,30,and60mg/kg.

Fasting

bloo

d glu

cose (m

g/dL)

Blood glu

cose (m

g/dL)

AUC in

OGTT (m

g/dL-h)

600

500

400

300

200

100

0

600

500

400

300

200

100

0

1200

1000

800

600

400

200

0

NR DM DM 10 30 60

0 20 40 60 80 100 120 140 160

NR DM DM 10 30 60

Time (min)

Pio DM+UMB (mg/kg)

Pio DM+UMB (mg/kg)

Normal rat

DM rat

DM+Pio

DM+UMB 10

DM+UMB 30

DM+UMB 60


Effect of UMB on OGTT

Todeterminetheinsulinsensitizingeffectof

UMB,OGTTtreatmentwasperformedatthefifthweek

oftreatment.Oraladministrationwithglucosecauseda

gradualincreaseinbloodglucoseinallthegroupsat30

min(Figure1B).Indiabeticcontrolgroup,thebloodglu-

cosewasremainedatthehighleveluntilat120min.As

comparedtothediabeticcontrolrats,theUMB(30mg/

kg)orpioglitazone(10mg/kg)significantly(p<0.05)sup-

pressedthebloodglucoselevelat60and120min.For

thelowestconcentrationofUMB(10mg/kg),itsignificantly

(p<0.05)decreasedbloodglucoseonlyat120min.Con-

sistentwiththeAUCofbloodglucoselevelafterglucose

administration,whichwashigherindiabeticcontrolthan

thatofnormalcontrolrats,andwasdecreasedby10and

30mg/kgUMBtreatments(Figure1C).

Aorta

MDA

(nmol/mg protein

)He

art M

DA (n

mol/mg protein

)

10

8

6

4

2

0

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0

NR DM DM 10 30 60

NR DM DM 10 30 60

Pio DM+UMB (mg/kg)

Pio DM+UMB (mg/kg)

A

B


Figure 2EffectofUMBonMDAproductioninthoracicaorta(A),heart(B),kidney(C)andliver(D)inhigh-fatdiet/

streptozotocin-inducedtype2diabeticrats.Valuesweremean±S.E.M.(n=6).*p<0.05whencomparedtonormal

controlgroup;#p<0.05whencomparedtodiabeticcontrolgroup.NR:normalcontrolrattreatedwith5%Gum

Arabic;DM:diabeticcontrolrattreatedwith5%GumArabic;DM+Pio:diabeticrattreatedwithpioglitazone10

mg/kg;DM+UMB:diabeticrattreatedwithumbelliferone10,30,and60mg/kg.

Kidney M

DA (n

mol/mg protein

)Liv

er M

DA (n

mol/mg protein

)

0.30

0.25

0.20

0.15

0.10

0.05

0.00

2.5

2.0

1.5

1.0

0.5

0.0NR DM DM 10 30 60

NR DM DM 10 30 60

Pio DM+UMB (mg/kg)

Pio DM+UMB (mg/kg)

C

D


Effect of UMB on serum lipid profiles

AsshowninTable1,thereweresignificant

(p<0.05)increasesintotalcholesterol,triglyceride,and

NEFAlevelsintheserumofdiabeticcontrolascompared

tonormalcontrolrats.However,thediabeticrattreated

withUMB(10,30,and60mg/kg)orpioglitazonehadthe

significantdecreasesintotalcholesterol,triglyceride,and

NEFA.

Serum parameters

Group of treatment Total cholesterol (mg/dL) Triglyceride (mg/dL) NEFA (mg/dL)

Normalcontrol 71.3± 4.1 155.5± 1.6 26.6± 1.1

Diabeticcontrol 127.4± 9.4* 253.1± 9.9* 54.4± 3.4*

Diabetic+Pio10 87.3± 5.3# 158.7± 8.7# 26.3± 3.4#

Diabetic+UMB10 89.9± 3.8# 171.3± 8.1# 28.0± 1.2#

Diabetic+UMB30 85.4± 6.4# 162.4± 8.5# 27.5± 1.2#

Diabetic+UMB60 91.0± 4.1# 174.7± 1.9# 30.4± 4.5#

Table 1 EffectofUMBonserumtotalcholesterol,triglyceride,andNEFAinhigh-fatdiet/streptozotocin-inducedtype2

diabeticrats.

Valuesweremean± S.E.M.(n=6).*p<0.05whencomparedtonormalcontrolgroup;#p<0.05whencomparedtodiabeticcontrolgroup.NR:normalcontrolrattreatedwith5%GumArabic;DM:diabeticcontrolrattreatedwith5%GumArabic;DM+Pio:diabeticrattreatedwithpioglitazone10mg/kg;DM+UMB:diabeticrattreatedwithumbelliferone10,30,and60mg/kg.

Effect of UMB on lipid peroxidation content

TheMDAcontentsinserum(Table2),thoracic

aorta,heart,kidneyandliver(Figure2A,2B,2C,and2D,

respectively)ofdiabeticratsweresignificantlyincreased

ascomparedtothenormalrats(p<0.05).Itisnotewor-

thythatthediabeticratsreceivingalldosesofUMBhad

significantlylowerlevelofMDAinalltissuethanthatof

diabeticcontrolrats.

Effect of UMB on serum TNF-α and MCP-1 levels

AsshowninTable2,thediabeticratshadsignifi-

cantlyincreasedTNF-αandMCP-1levels.However,after

treatmentwithalldosesofUMB,thelevelsofTNF-α and

MCP-1weresignificantlyreduced.ThedecreasesinTNF-α

andMCP-1by30mg/kgUMBwascomparableto10

mg/kgpioglitazone.


Discussion and conclusion Themajorfindingsofthepresentworkwerethat

thedailysupplementationwithUMBcoulddecreaseblood

glucose,improveglucosetolerance,anddecreaselipid

profiles,MDAinflammatorycytokinesinHFD/STZ-induced

T2DMrats.

TheratsthatreceivedHFDandlowdoseof

STZ(35mg/kg)hadthehyperglycemicstateandimpaired

glucosetolerance.Thismodelalsoshowedabnormalities

oflipidmetabolismbyincreaseinserumtotalcholesterol,

triglycerideandNEFA,whicharesimilartothemetabolic

changesinhumanwithT2DM.Allmetabolicchangesinour

diabeticanimalmodelwereconsistentwiththeprevious

reportsfromotherstudies24-26.

TounderstandthepharmacologicaleffectofUMB,

wefirststartedtoanalyzeitseffectonbloodglucoseand

lipidprofiles.Weobservedthatthehighbloodglucosein

diabeticratswasdecreasedbyUMBtreatment.Inparticu-

lar,UMBat30mg/kgnotonlydecreasedtheFBG,butalso

remarkablyimprovedtheglucosetolerance.Severalstudies

suggestedthatabnormalbloodlipidswerecharacteristicof

casewithinsulinresistance,especiallyhighcirculatingfree

fattyacids27-28.SurprisinglyalldosesofUMBtreatment

effectivelyreducedtheserumtotalcholesterol,triglyceride

andNEFAlevels.

Therearemarkeddifferencesincoumarinme-

tabolismbetweensusceptiblerodentandotherspecies.

Themajorrouteofcoumarinmetabolisminmurinesisby

a3,4-epoxidationpathway,whichresultsintheformation

oftoxicmetabolites29.Thesetoxicmetabolitesmightbea

negativeimpactonglucoseandlipidmetabolismsinT2DM

ratmodel.Althoughreportsofadverseeffectsinhumans

resultingfromcoumarinadministrationarerare,itisacutely

toxictolaboratoryanimalsinchronicoralgavageadministra-

tionatdosesequalorhigherof200mg/kg30.Therefore,it

ispossiblethatthehighdoseofUMB(60mg/kg)isless

effectivethanotherdosesinregulatingthehyperglycemic

condition.However,inourstudydidnotobserveanysigns

oftoxicityinalldosesofumbelliferone-treatedrats.

Hyperglycemiaisthemaincauseofcomplications

ofdiabetesbecauseelevatedglucoseconcentrationdirectly

injurescellsandinduceslipidperoxidation31.Therefore,

wefurtheranalyzedtheeffectofUMBonlipidperoxide

alteration.DiabeticratstreatedwithUMBhadasignificantly

lowerMDAconcentrationintheserumandalsoinvarious

tissuesespeciallyintheaortictissuethanthatofnon-

treateddiabeticrats(Figure2A).Thesignificantlyincreased

MDAconcentrationsinserumandvarioustissuesinchronic

diabeticratspointtoROS-mediatedcellulardamage,denot-

ingthepresenceofoxidativestressinchronicdiabetes3.

Serum parameters

Group of treatment MDA (nmol/L) TNF-α (pg/mL) MCP-1 (pg/mL)

Normalcontrol 226.5±3.2 14.9±0.2 252.2±5.0

Diabeticcontrol 310.0±5.5* 21.2±0.3* 430.4±7.2*

Diabetic+Pio10 239.5±7.4# 17.0±0.2# 253.6±2.6#

Diabetic+UMB10 246.0±4.3# 18.2±0.3# 269.6±15.6#

Diabetic+UMB30 237.5±2.0# 17.8±0.1# 264.7±7.8#

Diabetic+UMB60 253.6±5.5# 18.2±0.3# 280.0±8.7#

Valuesweremean±S.E.M.(n=6).*p<0.05whencomparedtothenormalcontrolgroup;#p<0.05whencomparedtothediabeticcontrolgroup.Normalcontrol:normalcontrolrattreatedwith5%GumArabic;Diabeticcontrol:diabeticcontrolrattreatedwith5%GumArabic;DM+Pio10:diabeticrattreatedwithpioglitazone10mg/kg;DM+UMB:diabeticrattreatedwithumbelliferone10,30,and60mg/kg

Table 2EffectofUMBonserumMDA,TNF-α,andMCP-1inhigh-fatdiet/streptozotocin-inducedtype2diabeticrats.


Thus,thetreatmentthataimsatreducingoxidativestress

willbebeneficialinpatientswithT2DM.

IthasbeenproposedthatT2DMisadisease

oftheimmunesystem,involvingacytokine-mediated

acute-phaseinflammatoryresponse32.Astudyin3T3-L1

adipocytesculture,ithasbeenshownthatinsulinresis-

tanceassociatedmediators,suchasTNF-α,IL-6,and

growthhormonehaveasignificantstimulatoryeffecton

MCP-1secretion33.OurresultsshowedthatUMBefficiently

reducedTNF-αandMCP-1levelindiabeticrats,whereas

itdecreasedthehighbloodglucoseandimprovedglucose

tolerance.

Ashighbloodglucoselevelcancauseincrease

inoxidativestressandinflammation.Thehypoglycemic,

hypolipidemic,antioxidant,andanti-inflammatoryactivities

ofUMBmaybeassociatedtoeachother.Therefore,

administrationofUMBcouldbehelpfulinnotonlyreducing

thehighbloodglucosebutmightdelaythecomplicationof

diabetesbyreducingtheoxidativestressandinflammation.

Inconclusion,UMBisaprovenbeneficialcom-

poundfordiabeticstate.UMBnotonlyreducestheblood

glucosebutalsoreducestheoxidativestressandinflam-

mationprocesses.Eventually,UMBcanbeadministeredas

acomplementarytherapeuticregimen.

Acknowledgement Theauthorsgratefullyacknowledgethefinancial

supportprovidedbyThammasatUniversityundertheTU

ResearchScholar,ContractNo.2/28/2556.

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บทคัดย่อ

ฤทธิ์ลดระดับน�้ำตำลในเลือด ฤทธิ์ต้ำนออกซิเดชั่น และฤทธิ์ต้ำนกำรอักเสบ ของสำรอัมเบลลิเฟอโรนในหนูขำวเบำหวำนชนิดที่ ๒

ที่เหนี่ยวน�ำด้วยอำหำรไขมันสูงร่วมกับฉีดสเตร็ปโตโซโตซิน

จริญญาพร เนาวบุตร*, นันทิยา สมภาร*, ศุภเกต แสนทวีสุข**, พัชรีวัลย์ ปั้นเหน่งเพ็ชร***

*สาขาเภสัชวิทยาสถานวิทยาศาสตร์พรีคลินิกคณะแพทยศาสตร์มหาวิทยาลัยธรรมศาสตร์**สาขากายวิภาคศาสตร์สถานวิทยาศาสตร์พรีคลินิกคณะแพทยศาสตร์มหาวิทยาลัยธรรมศาสตร์***ภาควิชาเภสัชวิทยาคณะแพทยศาสตร์มหาวิทยาลัยขอนแก่นผู้ให้ติดต่ออาจารย์ดร.จริญญาพรเนาวบุตรสาขาเภสัชวิทยาสถานวิทยาศาสตร์พรีคลินิกคณะแพทยศาสตร์มหาวิทยาลัยธรรมศาสตร ์ อีเมล[email protected]

บทน�ำ: ภาวะเครยีดออกซเิดช่ันและการอกัเสบเรือ้รงัเป็นกระบวนการทางพยาธสิภาพทีส่�าคัญซึง่ก่อให้เกดิภาวะดือ้

ต่ออินซูลินและการเกิดโรคเบาหวานชนิดที่๒รวมทั้งภาวะแทรกซ้อนจากโรคนี้ส�าหรับการศึกษานี้

มีวัตถุประสงค์เพ่ือประเมินฤทธิ์ของสารอัมเบลลิเฟอโรนต่อการควบคุมระดับน�้าตาลในเลือดภาวะไขมันใน

เลือดสูงภาวะเครียดออกซิเดชั่นและกระบวนการอักเสบเรื้อรังในหนูขาวเบาหวานชนิดที่๒

วิธีกำรศึกษำ: น�าหนูขาวเพศผู้สายพันธุ์Wistarเหนีย่วน�าให้เป็นเบาหวานชนิดที่๒ดว้ยการให้หนูไดร้ับอาหารไขมนัสงูนาน

๓สปัดาห์จากนัน้ฉดีสารสเตรป็โตโซโตซนิ(ขนาด๓๕มลิลกิรมัต่อน�า้หนกัตวั๑กโิลกรมั)เพ่ือท�าลายตบัอ่อน

วธิกีารดงักล่าวท�าให้หนทูีม่รีะดบัน�า้ตาลในเลอืดสงูกว่า๑๒๖มลิลกิรมัต่อเดซลิติรจะได้รบัด้วยสารอมัเบลลเิฟอโรน

นาน๖สัปดาห์เพ่ือตรวจวัดระดับน�้าตาลในเลือดค่าไขมันค่าmalondialdehyde(MDA)และสารอักเสบ

tumornecrosisfactor-α(TNF-α)andmonocytechemoattractantprotein-1(MCP-1)

ผลกำรศึกษำ: การเหนี่ยวน�าหนูขาวเบาหวานชนิดที่๒ด้วยวิธีนี้ท�าให้หนูมีระดับน�้าตาลในเลือดสูงการท�างานของอินซูลิน

บกพร่องมกีารเพ่ิมข้ึนของระดบัโคเลสเตอรอลไตรกลีเซอไรด์และกรดไขมนัอสิระในเลอืดระดบัMDAและ

สารอักเสบTNF-αและMCP-1ในเลือดสูงขึ้นผลการทดลองพบว่าสารอัมเบลลิเฟอโรนสามารถลดระดับ

น�้าตาลในเลือดเพ่ิมการท�างานของอินซูลินและลดระดับไขมันในเลือดนอกจากนี้สารอัมเบลลิเฟอโรน

ช่วยลดระดับMDAในเลือดและในเนื้อเยื่อต่างๆตลอดจนช่วยลดการหลั่งของTNF-αและMCP-1อีกด้วย

วิจารณ์และ ผลการทดสอบนีแ้สดงให้เหน็ว่าสารอมัเบลลิเฟอโรนสามารถลดระดบัน�า้ตาลในเลือดลดระดบัไขมนัสูงในเลอืด

สรุปผลกำรศึกษำ:ลดภาวะเครียดออกซิเดชั่นและลดการอักเสบในหนูขาวเบาหวานชนิดที่๒ได้

ค�าส�าคัญ:สารอัมเบลลิเฟอโรน,หนูเบาหวานชนิดที่๒,ภาวะเครียดออกซิเดชั่น,การอักเสบ

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