Identification and characterization of potent CYP2D6 inhibitors

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1、JournalofEthnopharmacology153(2014)190–196ContentslistsavailableatScienceDirectJournalofEthnopharmacologyjournalhomepage:www.elsevier.com/locate/jepIdentificationandcharacterizationofpotentCYP2D6inhibitorsinlotusleavesLin-HuYe,Xiao-XiHe,Ling-TiKong,Yong-HongLiao,Rui-LePan,Bi

2、ng-XinXiao,nXin-MinLiu,QiChangInstituteofMedicinalPlantDevelopment,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege,Beijing100193,ChinaarticleinfoabstractArticlehistory:Ethnopharmacologicalrelevance:Theherboflotus(Nelumbonucifera)leavesisacommonlyusedReceived22No

3、vember2013traditionalChineseherbalmedicinethatisutilizedforthetreatmentofsunstroke,toassuagethirst,ReceivedinrevisedformandtocurebothdiarrheaandfeverinChina.Modernpharmacologicalstudieshavedemonstratedthat25January2014theherbexhibitsvariouspharmacologicaleffects,suchasanti-

4、hyperlipidemia,anti-obesity,anti-oxidant,Accepted8February2014anti-HIV,anti-microbial,andanti-hypoglycemicactivities.Currently,theherbisbecomingmorepopularAvailableonline21February2014inChinaasa“teadrink”orasamainingredientofsomeherbalformulations,whichimpliesthattheherbKey

5、words:and/oritsproductsarenowmorelikelytobeconcurrentlyadministeredwithconventionalmedicinesforNelumbonuciferalosingbodyweightandreducingbloodlipids.However,itspotentialinhibitoryeffectonhumanCytochromeP450cytochromeP450(CYP)hasnotbeensystemicallyinvestigatedtodate.Theprese

6、ntstudywasperformedHerb–druginteractionstoassessthepotentialinhibitoryeffectsoflotusleafalcoholicextract(LAE),itsmajorfractions,anditsMechanism-basedinhibitionmaincompoundsonfiveCYPisoenzymes(CYP2C9,CYP2C19,CYP2D6,CYP2E1,andCYP3A4)invitro.Materialandmethods:Fiveprobesubstrat

7、eswereincubatedwithhumanlivermicrosomesinthepresenceorabsenceoftheLAE,thealkaloidfraction(AF),theflavonoidfraction(FF),ortheindividualaporphinealkaloids,namely,nuciferine(NF),N-nornuciferine(N-NF),and2-hydroxy-1-metho-xyaporphine(HMA).Aftertheincubation,therelativemetabolite

8、softhesubstrateswereanalyzedusingLC–MS/MS.Results:TheresultsshowedthattheLAEstrong