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Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEHesperetinCat.No.:HY-N0168CASNo.:520-33-2分⼦式:C₁₆H₁₄O₆分⼦量:302.28作⽤靶点:p38MAPK;Autophagy;Apoptosis作⽤通路:MAPK/ERKPathway;Autophagy;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(330.82mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.3082mL16.5410mL33.0819mL5mM0.6616mL3.3082mL6.6164mL10mM0.3308mL1.6541mL3.3082mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;⼀旦配成溶液,请分装保存,避免反复冻融造成的产品失效。储备液的保存⽅式和期限:-80°C,6months;-20°C,1month。-80°C储存时,请在6个⽉内使⽤,-20°C储存时,请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液,再依次添加助溶剂:(为保证实验结果的可靠性,澄的储备液可以根据储存条件,适当保存;体内实验的⼯作液,建议您现⽤现配,当天使⽤;以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂:10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(8.27mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂:10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.27mM);Clearsolution3.请依序添加每种溶剂:10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.27mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Hesperetin⼀种天然烷酮类物质,为有效的,⼴谱的⼈UGT抑制剂。Hesperetin可调节凋亡途径。体外研究Hesperetinhastheretentionofantioxidantpotentialinselfnano-emulsifyingdrugdeliverysystem[1].HesperetinandNGRdisplaybroad-spectruminhibitionagainsthumanUGTs.Besides,HesperetinexhibitsstronginhibitoryeffectsonUGT1A1,1A3and1A9(bothIC50andKivalueslowerthan10µM)andmoderatelyinhibitsUGT1A4,UGT1A7,UGT1A8(IC50values29.68-63.87µM)[2].Hesperetininteractswithdifferenttypesofproteinsinvolvinghydrogenbonds,pi-pieffects,pi-cationbondingandpi-sigmainteractionswithvaryingbindingenergies.Hesperetinexhibitsdrug-likepropertieswhichprojectsitspotentialasatherapeuticoptionforCHIKVinfection[3].Hesperetindose-dependentlyreducesGCDCA-inducedcaspase-3activityinculturedprimaryrathepatocytes.Hesperetinalsodose-dependentlyreducesCM-inducedNos2(iNOS)expressioninhepatocytes.Interestingly,hesperetin-inducedexpressionoftheantioxidantgenehaemoxygenase1(HO-1)aboutfourfoldcomparedwithcytokinemixturealone[5].体内研究PreadministrationofHesperetin(40mg/kgb.w.,oral)significantlyattenuatestheCd-inducedoxidativestressandmitochondrialdysfunction,restorestheantioxidantandmembrane-boundenzymeactivitiesanddecreasesapoptosisinthebrainofrats[4].Hesperetin(200mg/kg)attenuatesConA-inducedhepatocyteapoptosisandhepaticNos2(iNOS)expressioninmice.Hesperetinco-treatmentalsodecreasestheoccurrenceofapoptoticbodies,hydropicdegeneration,nuclearfragments,autolysisandhaemorrhage.ThenumberofleukocytesinfiltratedinlivertissueofmicewithD-GalN/LPS-inducedfulminanthepatitisaresignificantlydecreasedbyhesperetininamurinemodel[5].PROTOCOLKinaseAssay[4]First,0.5mLtissuehomogenateisdilutedwith1mLwater.Then,tothismixture,2.5mLethanoland1.5mLchloroform(allreagentschilled)areaddedandshakenfor1minat4°C,thencentrifuged.Theenzymeactivityinthesupernatantisdetermined.Theassaymixturecontained1.2mLsodiumpyrophosphatebuffer(0.025M,pH8.3),0.1mL186mMphenazinemethosulfate(PMS),0.3mL30mMNitrobluetetrazolium(NBT),and0.2mLofnicotinamideadeninedinucleotide(NADH),andappropriatelydilutedenzymepreparationandwaterinatotalvolumeof3mL.ReactionisinitiatedbytheadditionofNADH.Afterincubationat30°Cfor90min,thereactionisstoppedbytheadditionof1mLglacialaceticacid.Thereactionmixtureisstirredvigorouslyandshakenwith4mLn-butanol.Theintensityofthechromogeninthebutanollayerismeasuredat560nmagainstabutanolblank.Asystemwithoutenzymeservedascontrol.Oneunitofenzymeactivityisdefinedas50%inhibitionofNBTreductionin1minundertheassayconditions.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalAfter7daysofadjusting,theanimalsarerandomlydividedinto10experimentalgroups.Controlgroup(n=8):Administration[4]TheseanimalsaretreatedwiththeequivalentvolumeofPBSasusedfortheadministrationofConAandD-GalN/LPS.Controlhesperetingroup(n=8):Themicearetreatedwithhesperetin400mg/kgp.o.in0.5%sodiumcarboxymethylcellulose(CMC-Na)solutionfor10days.ConAgroup(n=15):TheanimalsaretreatedwiththesamevolumeofCMC-Naasusedforadministrationofhesperetinfor10daysandarechallengedwithConA(i.v.15mg/kg).ConA+hesperetingroups:Theanimalsreceivevariousdosesofhesperetin(100,200,400mg/kg)p.o.for10daysbeforeConAinjection(eachgroupn=15).D-GalN/LPSgroup(n=15):TheanimalsaregivenCMC-Nafor10daysandinjectedi.p.withD-GalN(700mg/kg)/LPS(5μg/kg).D-GalN/LPS+hesperetingroups:Threedosesofhesperetin(100,200,400mg/kg)aregiventomiceoncedailyfor10days.D-GalN(700mg/kg)/LPS(5μg/kg)areinjectedi.p.(eachgroupn=15).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•ActaPharmSinB.2021Jan;11(1):143-155.•Antioxidants(Basel).2022,11(11),2093.•IntJMolSci.2022Sep7;23(18):10346.•EurJPharmacol.2019Jun5;852:151-158.•ReprodBiolEndocrinol.2020Oct12;18(1):100.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].AryaA,etal.Bioflavonoidhesperetinovercomebicalutamideinducedtoxicitybyco-deliveryinnovelSNEDDSformulations:Optimization,invivoevaluationanduptakemechanism.MaterSciEngCMaterBiolAppl.2017Feb1;71:954-964[2].LiuD,etal.InhibitoryEffectofHesperetinandNaringeninonHumanUDP-GlucuronosyltransferaseEnzymes:ImplicationsforHerb-DrugInteractions.BiolPharmBull.2016;39(12):2052-2059.[3].OoA,etal.Insilicostudyonanti-Chikungunyavirusactivityofhesperetin.PeerJ.2016Oct26;4:e2602.eCollection2016.[4].
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