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1 (27): [22]SerceOGursoyTOvaliFetal.EfectsofSaccharomyces boulardi on Neonatal Hyperbilirubinemia: A Randomized ControledTrial[J].AmJPerinatol201530(2): [23]. trialofeficacyandsafety[j].indianjpediatr201279(2): [J] (6): [24]DemirelGCelikIHErdeveOetal.Impactofprobioticson thecourseofindirecthyperbilirubinemiaandphototherapydu- rationinverylow birth weightinfants[j].j Matern Fetal NeonatalMed201326(2): [27]AmitaiYRegev MAradIetal.Treatmentofneonatalhy- perbilirubinemiawithrepetitiveoralactivatedcharcoalasan adjuncttophototherapy[j].jperinatmed199321(3): [28]CuperusFJSchreuder ABvanImhofDEetal.Beyond plasmabilirubin:theefectsofphototherapyandalbuminon brainbilirubinlevelsin Gunnrats[J].J Hepatol (1): [29]Shahian MMoslehiMA.Efectofalbuminadministrationpri- ortoexchangetransfusionintermneonateswithhyperbilirubi- nemia-arandomizedcontroledtrial[j].indianpediatr (3): [42]ChenSPTianLLLiuFL.ClinicalobservationofYinzhi- [30]. [J]. [J] (2): (14): ingsulfonamidesneartermandneonataljaundice[j].obstet Gynecol (1): [32] Berkovitch M1Uziel YGreenberg Retal.False-high bloodsalicylatelevelsinneonateswithhyperbilirubinemia[j]. TherDrug Monit200022(6): [31]KlarskovP1AndersenJTJimenez-Solem Eetal.Short-act- [33] ValaesTKipouros KPetmezakiSetal.Efectivenessand safetyofprenatalphenobarbitalforthepreventionofneonatal- jaundice[j].pediatrres198014(8): [34] MurkiSDutaSNarang Aetal.Arandomizedtriple- blindplacebo-controledtrialofprophylacticoralphenobarbi- taltoreducetheneedforphototherapying6pd-deficientneo- nates[j].jperinatol200525(5): [35] Chawla DParmar V.Phenobarbitoneforprevention and treatmentofunconjugatedhyperbilirubinemiainpreterm neo- nates:asystematicreviewandmeta-analysis[j].indianpedi- atr200947(5): [36]. [J] (5):4-7. brateinjaundiceofhealthytermneonates:randomisedclinical [38]XiongTChenDDuanZetal.Clofibrateforunconjugated hyperbilirubinemiainneonates:asystematicreview[j].indian Pediatr201249(1): [39]ZahedpashaYAhmadpour-Kacho MHajiahmadiMetal. caltherapiesforunconjugated hyperbilirubinemia[j].curr Pharm Des200915(25): [41]. [J] (9): [37]FalahRIslamiZLotfiSR.Singledoseof50 mg/kgclofi- [25]. [J]. Eficacyofclofibrateonsevereneonataljaundiceassociated (6): withglucose-6-phosphatedehydrogenasedeficiency(arandom- [26]. [J]. izedclinicaltrial)[j].southeast AsianJ Trop Med Public (3): Health200839(3): [40]CuperusFJHafkampAMHulzebosCetal.Pharmacologi- huangoralliquidon prevention oftheprematureinfantile jaundice[j].chinjintegrmed200915(4): [43]. [J] (25): [44]. ABO 158. [45]. [J] (6): [46]. [J] (5): rubin[j].indianjpediatr200875(4): [48]. [J]. 2010(9): [49]. [J] (8): [50]AoshimaNFujieYItohTetal.Glucoseinducesintestinal human UDP-glucuronosyltransferase (UGT)1A1toprevent neonatalhyperbilirubinemia[j].scirep20144:6343. [51]. 39 [J] (11): [ ] ( ; ; ) [ ] : [47]Nassirian HEslamiST.Efectsofchichoriumintybusonbili- [ ] ( :2012I1001) [ ] : : E- [ ] : : sohoto

2 1520 : : : [ ] ; ; ; [ ]R99 [ ]B [ ] (2015) DOI: /j.cnki.chinhosppharmacyj ResearchprogressoftoxicitymechanismofTripterygiumwilfordi HAO Xia 12 WANGZhong-zhen 13 LINBing 1 LIU Zhi-hong 1 SONG Hong-tao 1 (1.DepartmentofPharma- cyfuzhougeneralhospitalofnanjing MilitaryRegionFujianFuzhou350025China;2.MedicalColegeXiamenUniversi- tyfujianxiamen361102china;3.fujianuniversityoftraditionalchinesemedicinefujianfuzhou350025china) ABSTRACT:OBJECTIVE ToupdaterecentprogressintoxicmechanismofTripterygium wilfordidiscussrelationshipbe- tweenitstoxicityandconstituentsandprovideaguidanceforrationaldruguseinclinicalpractice.methods Byreferringto recentliteraturesathomeandabroadsystematicalytoxicmechanismoftripterygium wilfordiwasreviewed.results Toxicityoftripterygium wilfordiwasinvolvedinmultipleorgansandsystemsandtoxiccomponentswerealsoconsideredas efectivecomponents.researchontoxicmechanismoftripterygium wilfordiishelpfultodeveloppreparationsofhighefi- ciencyandlowtoxicityandprovideaguidanceforrationaldruguseinclinicalpractice.conclusion Toxicmechanismof Tripterygium wilfordihasbecomeafocusandsomeprogresseshavebeenachieved.howeverstudiesonacionmechanism arestilnotcompleteandsystemicfortripterygium wilfordiduetocomplexityofitschemicalcomponentsandintegrityof TCM pharmacologyandfurtherstudiesarestilneeded. KEY WORDS:Tripterygium wilfordi HooK.F.;toxicity;mechanism;per-oxidation;apoptosis 14% 10.9% (Tripterygium wilfordi HooK. F.) 4.1% 14.1% 1 ( ) ( [3] [4] ) ( ) (P<0.01) (P<0.01) [1] % [2] [3] % 16.7% [5] 15%

3 2.1 Ni [6] [3] (ALP) SD 4.1 HepG2 [12] Nrf2 Wang [13] 1000μg DNA kg -1 Wistar 14d [8] 97 Herc4 Mrto4 Ipo GSH/GSSG Fasl Bax NF-κB 4.2 Wang [13] 1000μg Wnt4 c-jun kg -1 Wistar 14d AST ALP γ-ggt : : [9] camp/pka Gck PCk1 Aldob G6pc Fbp2 Pygl [10] ; Pklr ; 4.3 Fas Bax Bcl-2 Fas (FasL) [14] Fas 3 Bid Bax Bad Bcl-2 Bax Bcl-2 [3] [11] Bad 6810 μg ml -1 Bid (P<0.01) [15-16] Mei [17] IC Bcl-2 Bax 72h μg ml -1 2 G 0 /G 1 S DNA caspase3 caspase3 caspase9 caspase9 caspase3 4.4 Shen [18] - CYP3A CYP3A 4 5 DNA 33 >CYP3A2>CYP1A2>CYP2E1>CYP2D6 (ALT) (AST) [13] 1521 Sun [19] CYP CYP2C11

4 BALB/C 1.2mg kg -1 1d (BUN) (Cre) [2] 5.1 ROS Bax/Bcl-2 CYPC Yang [20] SD caspase3 1 mg kg -1 7 SOD GSH-Px (P<0.05) Zhou [24] H9c2 ROS [25] 783 (MDA) (P<0.05) Cre BUN 10 HE TUNEL : VitC Liu [26] SD SOD GSH-Px 28d MDA 400μg kg -1 [21] 5.2 ; Bax Bid Bad (P<0.01)Bcl- 2 Bax Bcl-2 CYP450 CYP3A2 (P<0.01) Fas FasL 8 (P<0.01) Fas/ : FasL 5.3 Sun [22] Wistar ; ; Zonu- laoccludens1 ; FITC- DNA BUN Cre 6 [3] [23] Q-T QRS S-T ST ;

5 (1): chung200758(12): [13] WangJYJiangZZLiJZetal.Geneexpressionprofiling andpathwayanalysisofhepatotoxicityinducedbytripyolidein Wistarrats[J].FoodandChemicalToxicology201358(8): Herc4 Ipo11 Mrto4 [J] (9): [23] [9] [D] LiuJJiangZZLiuLetal.Triptolideinducesadverseefect onreproductiveparametersoffemalesprague-dawleyrats[j]. [24]ZhouJXiCWang Wetal.Triptolide-inducedoxidative DrugandChemicalToxicology201134(1):1-7. stressinvolvedwithnrf2contributetocardiomyocyteapopto- sisthroughmitochondrialdependentpathways[j].toxicology [10]ZhangJLiuLMuXMetal.Efectoftriptolideonestradi- leters (3): olreleasefrom culturedratgranulosacels[j].endocrine [25]. Journal201259(6): [J]. [11] (9): [D] [26]LiuLJiangZLiuJetal.Sexdiferencesinsubacutetoxic- ityandhepaticmicrosomalmetabolismoftriptolideinrats[j]. [12]JiaLiFeihaiShenCuiwenGuanetal.ActivationofNrf2 Toxicology (1): ProtectsagainstTriptolide-Induced Hepatotoxicity [J].PLoS [ ] ONE20149(7): [14]KaufmannTStrasserAJostPJ.Fasdeathreceptorsigna- [8]. ling:rolesofbidandxiap[j].celdeathand Diferentia- tion201219: [15]CrokerBAO'DonnelJANowelCJetal.Fas-mediated neutrophilapoptosisisacceleratedbybidbakandbaxand inhibitedbybcl-2and Mcl-1[J].ProceedingsoftheNational AcademyofSciences (32): [16]HowelsCCBaumann WTSamuelsDCetal.TheBcl-2-as- sociateddeathpromoter(bad)lowersthethresholdatwhich thebcl-2-interactingdomaindeathagonist(bid)triggersmi- tochondriadisintegration[j].journaloftheoreticalbiology [17]MeiZLiXWuQetal.Theresearchontheanti-inflamma- : toryactivityandhepatotoxicityoftriptolide-loadedsolidlipid [1]. nanoparticle[j].pharmacologicalresearch200551(4):345- [J] (5): [2] [18]ShenGZhuangXXiao. Wetal.RoleofCYP3Ainregula- [J] (2): tinghepaticclearanceandhepatotoxicityoftriptolideinratliv- [3]. 294 er microsomesandsandwich-culturedhepatocytes[j].food [J]. andchemicaltoxicology201471(9): (1): [4]. [19]Sun MTangYDingTetal.Inhibitoryefectsofcelastrol [J] (2): onratlivercytochromep4501a22c112d62e1and3a2 activity[j].fitoterapia201492(1): [20] [5]. Yang FRen LZhuo Letal.Involvementofoxidative [J] (3): stressinthemechanismoftriptolide-inducedacutenephrotox- icityinrats[j].experimentaland Toxicologic Pathology (7): [21]. C [D].. [J] (10): [22]SunLLiHHuangXetal.Triptolidealtersbarrierfunc- tioninrenalproximaltubularcelsinrats[j].toxicologylet- ters (1): [6] NiBJiangZHuangXetal.Malereproductivetoxicityand toxicokineticsoftriptolidein rats[j]. Arzneimitel-Fors-

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