Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHesperetinCat.No.:HY-N0168CASNo.:520-33-2分?式:C??H??O?分?量:302.28作?靶點(diǎn):p38MAPK;Autophagy;Apoptosis作?通路:MAPK/ERKPathway;Autophagy;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(330.82mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.3082mL16.5410mL33.0819mL5mM0.6616mL3.3082mL6.6164mL10mM0.3308mL1.6541mL3.3082mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(8.27mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.27mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.27mM);ClearsolutionBIOLOGICALACTIVITY?物活性Hesperetin?種天然烷酮類物質(zhì)，為有效的，?譜的?UGT抑制劑。Hesperetin可調(diào)節(jié)凋亡途徑。體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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].