title: Ginkgolide B promotes proliferation and functional activities of bone marrow-derived endothelial progenitor cells: involvement of Akt/eNOS and MAPK/p38 signaling pathways.
abstract: Bone marrow-derived, circulating endothelial progenitor cells (EPCs) contribute to neovascularization in various diseases, and represent a very interesting alternative cell source for enhancing vasculogenesis in regenerative medicine. In this study, we investigated the effects of Ginkgolide B (GB) on proliferation and differentiation of EPCs, and the involved signaling pathway in vitro. EPC proliferation, migration, adhesion and angiogenesis activities were assessed with the WST-8 assay, Transwell chamber assay, cell counting and angiogenesis kit, respectively. Apoptosis was detected with annexin V and propidium iodide staining. The protein expression of angiogenesis-related makers was detected by Western blot, and related gene expression was determined by real-time polymerase chain reaction (RT-PCR). The results showed that GB promoted the proliferation and endothelial gene expression, and markedly enhanced vascular endothelial growth factor-induced migration response and the capability to incorporate into the vascular networks in EPCs. GB protected EPCs from H2O2-induced cell death. GB induced the phosphorylation of eNOS, Akt and p38, which in turn promoted cell proliferation and function. In conclusion, the present study demonstrates that GB, at a near medical applied dose, increases the number and functional activities of EPCs with involvement of Akt/endothelial nitric oxide synthase and mitogen-activated protein kinase (MAPK)/p38 signal pathways. These ﬁndings raise the intriguing possibility that GB may play an important role in the protection and revascularization of blood vessels.
authors.affiliation: Department of Pharmacy, Orthopaedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, PR China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Tang
authors.forename: Baoding
authors.initials: B
authors.lastname: Huang
authors.forename: Laibao
authors.initials: L
authors.lastname: Sun
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Peng
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Xuenong
authors.initials: X
authors.lastname: Zou
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D046934:Ginkgolides / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D009336:Necrosis; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D046934:Ginkgolides; D006861:Hydrogen Peroxide; D007783:Lactones; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D048051:p38 Mitogen-Activated Protein Kinases; D000099152:Cadherin 5; C467484:VEGFA protein, human; C045856:ginkgolide B; C496314:NOS3 protein, human