Water Extract of Korean Red Ginseng Stimulates Angiogenesis by Activating the PI3K/Akt-Dependent ERK1/2 and eNOS Pathways in Human Umbilical Vein Endothelial Cells(Molecular and Cell Biology)

概要

論文の詳細を見る
Angiogenesis is important for promoting cardiovascular disease, wound healing, and tissue regeneration. We investigated the effects of Korean red ginseng water extract (KRGE) on angiogenesis and its underlying signal mechanism. KRGE increased in vitro proliferation, migration, and tube formation of human umbilical vein en-dothelial cells, as well as stimulated in vivo angiogenesis without increasing VEGF expression. KRGE-inducedangiogenesis was accompanied by phosphorylation of ERK1/2, phosphatidylinositol 3-kinase (Akt), and endothe-lial nitric oxide synthase (eNOS) as well as an increase in NO production. Inhibition of PI3K activity by wort-mannin completely inhibited KRGE-induced angiogenesis and phosphorylation of Akt, ERK1/2, and eNOS, indicating that PI3K/Akt activation is an upstream event of the KRGE-mediated angiogenic pathway. The MEK inhibitor PD98059 blocked KRGE-induced ERK1/2 phosphorylation without affecting Akt and eNOS activation. However, the eNOS inhibitor N^G-monomethyl-L-arginine effectively inhibited tube formation, but partiallyblocked proliferation and migration as well as ERK phosphorylation, without altering Akt and eNOS activation, revealing that the eNOS/NO pathway is partially involved in ERK1/2 activation. This study demonstrated that KRGE stimulates in vitro and in vivo angiogenesis through the activation of the PI3K/Akt-dependent ERK1/2 and eNOS signal pathways and their cross talk.
2007-09-01