title: Astragaloside IV stimulates angiogenesis and increases nitric oxide accumulation via JAK2/STAT3 and ERK1/2 pathway.
abstract: Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus in Traditional Chinese Medicine, has been widely used to treat ischemic diseases. However, the potential mechanism is this action is unclear. In this study, we tested the hypothesis that AS-IV might promote angiogenesis through multiple signaling pathways. Our data indicate that AS-IV treatment promotes umbilical vein endothelial cells (HUVEC) proliferation, migration, and tube formation. AS-IV treatment also activates JAK2/STAT3 and ERK1/2 signaling pathways, and up-regulates endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production. AS-IV-induced angiogenesis in HUVECs is significantly blocked by specific kinase inhibitors. Our study indicated that AS-IV is a key regulator of NO and angiogenesis through the JAK2/STAT3 and ERK1/2 pathways, which provides a mechanistic basis for the potential use of this compound in the treatment of clinical ischemic diseases.
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China. chenxhdoctor@live.cn.
authors.forename: Shi-Guang
authors.initials: SG
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Chen
authors.forename: Chuan-Hua
authors.initials: CH
authors.lastname: Yang
authors.forename: Xiao-Hu
authors.initials: XH
authors.lastname: Chen
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012503:Saponins; D014315:Triterpenes; D009569:Nitric Oxide; C052064:astragaloside A; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases