Biol. Pharm. Bull. 30(9) 1674—1679 (2007)

termed angiogenesis, is a fundamental step in a variety of physiological and pathological conditions including wound healing, embryonic development, chronic inflammation, tumor progression, and metastasis. The process of blood vessel growth can repair tissue damage such as arteriosclerosis, myocardial infarction, and limb ischemia and thus has provided a significant tool for therapeutic neovascularization. Angiogenesis is as an important process for supplying metabolic needs, such as nutrients, various growth factors, and molecular oxygen, to sites of tissue repair or regeneration. Therefore, angiogenic inducers such as basic fibroblast growth factor and vascular endothelial growth factor (VEGF) have been used for neovascularization of ischemic diseases, wound healing, and tissue regeneration. Panax ginseng C. A. MAYER is well known as the most important herbal medicine in traditional eastern Asia for more than 2000 years and is now one of the most extensively used botanical products in the world. Among the several kinds of Panax ginseng products, Korean red ginseng has the most potent multiple pharmacological actions for treating various human diseases including cardiovascular diseases, rheumatoid arthritis, and diabetes mellitus. The major active ingredients of ginseng are the triterpene glycosides known as ginsenosides, which have been studied extensively for their pharmacological effects. Ambiguously, pure ginsenosides have been reported to promote wound healing and inhibit tumor growth through opposing effects on angiogenesis. Presently, the use of whole ginseng products such as steamed ginseng (Korean red ginseng), ginseng powder, and ginseng extract as alternative medicine have seen resurgence in use in the United States and Europe as well as Asian countries. However, the angiogenic effects of Korean red ginseng water extract (KRGE) and its underlying mechanisms have not been clearly studied in vitro and in vivo. It has been shown that KRGE and its saponins possess multiple pharmacological actions for treating various diseases including wound healing, liver regeneration, cerebral ischemia, and hypertension, which are associated with endothelial cell dysfunction or dysregulation of angiogenesis. We here investigated the effect of KRGE on angiogenesis and its intracellular signal pathway in human umbilical vein endothelial cells (HUVECs). Our results show that KRGE stimulates angiogenesis in vitro and in vivo through activation of the phosphatidylinositol 3-kinase (PI3K)/Aktdependent ERK1/2 and eNOS pathways.