title: Biphasic effect of EGb761 on simulated ischemia-induced rat BMSC survival in vitro and in vivo.
abstract: OBJECTIVE
  The standardized extract from the leaves of Ginkgo biloba (EGb761) is applied as a phyto-pharmacon in therapy of diverse cardiovascular disorders. However, the effects of EGb761 on bone-marrow mesenchymal stem cells (BMSCs) transplanted into the ischemic myocardium currently remain uncertain. In this study, the dosage-effects of EGb761 on BMSC survival in vitro and in vivo were investigated.
  
  
  METHODS
  The ischemic microenvironment of rat BMSCs was simulated by hypoxia/serum deprivation (SD) and the rat myocardial infarction model was established. The rat BMSCs were cultured under hypoxia/SD or transplanted into the animal ischemic heart. The BMSC apoptosis was determined by FACS and TUNEL assay. Each apoptotic signal molecule's activity was assayed by immunoblot.
  
  
  RESULTS
  EGb761 showed a biphasic effect on the hypoxia/SD-induced BMSC apoptosis. Low concentration of EGb761 (10-100μg/ml) aggravated hypoxia/SD-induced apoptosis via Akt inactivation and an enhancement of caspase-9 and caspase-3 expressions, whereas high concentration of EGb761 (500-2000μg/ml) significantly prevented hypoxia/SD-induced BMSC apoptosis via the activated Akt and the inactivated caspase-9 and caspase-3. The animal study also indicated that the apoptotic index (AI) in the high concentration of EGb761 group was significantly lower than the low concentration of EGb761 group.
  
  
  CONCLUSIONS
  The biphasic effect of EGb761 is closely related to the PI3K-Akt and caspase-9 signaling pathways. The therapeutic concentration of EGb761 may be one of the vital factors determining the specific action of EGb761 on cell apoptosis. It is of significant clinical implication to investigate the mechanisms of the biphasic effect of EGb761.
authors: Center of Biological Research, Xuzhou Medical College, Xuzhou 221002, Jiangsu, China.
authors: Shibao
authors: S
authors: Li
authors: Derong
authors: D
authors: Tang
authors: Zhiwei
authors: Z
authors: Xue
authors: Zhifeng
authors: Z
authors: Zhang
authors: Xiaojing
authors: X
authors: Sun
authors: Yuepeng
authors: Y
authors: Liu
authors: Hongyan
authors: H
authors: Dong
authors: Xiaoxing
authors: X
authors: Yin
authors: Zhongming
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use*; D018515:Plant Leaves; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000096983:Ginkgo Extract
chemical_list: D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract