Direct Stimulation of Adult Neural StemProgenitor Cells In Vitro and Neurogenesis In Vivo by Salvianolic Acid B 英文参考文献.docVIP

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Direct Stimulation of Adult Neural StemProgenitor Cells In Vitro and Neurogenesis In Vivo by Salvianolic Acid B 英文参考文献.doc

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Direct Stimulation of Adult Neural StemProgenitor Cells In Vitro and Neurogenesis In Vivo by Salvianolic Acid B 英文参考文献

DirectStimulationofAdultNeuralStem/ProgenitorCells InVitroandNeurogenesisInVivobySalvianolicAcidB PengweiZhuang1,YanjunZhang1*,GuangzhiCui1,YuhongBian2,MixiaZhang1,JinbaoZhang1, YangLiu1,XinpengYang1,AdejobiOluwaniyiIsaiah1,YingxueLin1,YongboJiang1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Traditional Chinese Medicine Pharmacology, Chinese Materia Medica College, Tianjin UniversityofTraditionalChineseMedicine,Tianjin,China,2ChineseMedicalCollege,TianjinUniversityofTraditionalChineseMedicine,Tianjin,China Abstract Background: Smallmolecules havebeenshowntomodulate theneurogenesis processes.In searchfor newtherapeutic drugs,theherbsusedintraditionalmedicinesforneurogenesisarepromisingcandidates. Methodology and Principal Findings: We selected a total of 45 natural compounds from Traditional Chinese herbal medicineswhichareextensivelyusedinChinatotreatstrokeclinically,andtestedtheirproliferation-inducingactivitieson neuralstem/progenitorcells(NSPCs).ThescreeningresultsshowedthatsalvianolicacidB(SalB)displayedmarkedeffects ontheinductionofproliferationofNSPCs.WefurtherdemonstratedthatSalBpromotedNSPCsproliferationindose-and time-dependent manners. To explore the molecular mechanism, PI3K/Akt, MEK/ERK and Notch signaling pathways were investigated.CellproliferationassaydemonstratedthatLy294002(PI3K/Aktinhibitor),butneitherU0126(ERKinhibitor)nor DAPT(Notchinhibitor)inhibitedtheSalB-inducedproliferationofcells.WesternBlottingresultsshowedthatstimulationof NSPCswithSalBenhancedthephosphorylationofAkt,andLy294002abolishedthiseffect,confirmingtheroleofAktinSal BmediatedproliferationofNSPCs.Ratsexposedtotransientcerebralischemiaweretreatedfor4weekswithSalBfromthe 7thdayafterstroke.BrdUincorporationassayresultsshowedthatexposureSalBcouldmaintaintheproliferationofNSPCs aftercerebralischemia.Morriswatermazetestshowedthatdelayedpost-ischemictreatmentwithSalBimprovedcognitive impairmentafterstrokeinrats. Significance:SalBcouldmaintaintheNSPCsse