title: Notoginsenoside Ft1 promotes angiogenesis via HIF-1α mediated VEGF secretion and the regulation of PI3K/AKT and Raf/MEK/ERK signaling pathways.
abstract: Notoginsenoside Ft1 (Ft1) is a saponin isolated from Panax notoginseng, which has been used traditionally for the treatment of trauma injuries in East Asia. Here we show that Ft1 is a novel stimulator of angiogenesis. The results show that Ft1 induces proliferation, migration, and tube formation in cultured human umbilical vein endothelial cells (HUVECs). Ft1 increases translocalization of hypoxia-inducible factor-1α (HIF-1α) from cytoplasm to nuclei, where it binds to the vascular endothelial growth factor (VEGF) promoter, increasing the expression of VEGF mRNA and the subsequent secretion of the growth factor. Ft1 induces the activation of PI3K/AKT and Raf/MEK/ERK signaling pathways. Pharmacological inhibition with LY294002, wortmanin or PD98059 reduces Ft1-induced angiogenesis, indicating the important role played by these pathways. In addition, Ft1 induces phosphorylation of the mammalian target of rapamycin (mTOR), and siRNA-mediated mTOR knockdown decreases tube formation, proliferation, transport of HIF-1α into nuclei and VEGF mRNA expression in response to Ft1. Finally, in vivo, Ft1 promotes the formation of blood vessels in Matrigel plug and wound healing in mice. Taken together, the present results reveal that Ft1 stimulates angiogenesis via HIF-1α-mediated VEGF expression, with PI3K/AKT and Raf/MEK/ERK signaling cascades concurrently participating in the process.
authors: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
authors: Kaikai
authors: K
authors: Shen
authors: Lili
authors: L
authors: Ji
authors: Chenyuan
authors: C
authors: Gong
authors: Yibo
authors: Y
authors: Ma
authors: Li
authors: L
authors: Yang
authors: Yi
authors: Y
authors: Fan
authors: Maoqi
authors: M
authors: Hou
authors: Zhengtao
authors: Z
authors: Wang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects / Q000293:injuries; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D012503:Saponins; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C575719:notoginsenoside Ft1