Mechanism of angiogenic effects of saponin from Ginseng Radix rubra in human umbilical vein endothelial cells

Abstract

1 The effects of saponin from Ginseng Radix rubra on angiogenesis (tube formation) and its key steps (protease secretion, proliferation and migration) in human umbilical vein endothelial cells (HUVEC) were examined to elucidate the mechanism of the tissue repairing effects of Ginseng Radix rubra. The effect on a wound healing model was also studied. 2 Tube formation was measured by an in vitro system. The activity and immunoreactivity of tissue-type plasminogen activator (tPA) as a protease for angiogenesis and the immunoreactivity of its inhibitor, plasminogen activator inhibitor-i (PAI-1), were measured in conditioned medium of HUVEC stimulated for 24 h with saponin. Cell proliferation was measured by counting the cell numbers at 2-7 days after seeding. Migration was measured by Boyden's chamber method. The effect on wound healing was studied in the skin of diabetic rats. 3 Saponin at 10-100 gg ml-' significantly stimulated tube formation by HUVEC in a dose-dependent manner. Saponin in a similar concentration-range increased the secretion of tPA from HUVEC as estimated by immunoreactivity and enzyme activity. On the other hand, PAI-1 immunoreactivity was slightly increased at 10 gg ml-' of saponin, but then was significantly decreased at 50 and 100 jig ml-'. Cell proliferation was only slightly enhanced by 1-100 jg ml-' of saponin, but migration was significantly enhanced by 10-100 jg ml-' in a dose-dependent manner. Moreover, saponin stimulated wound healing with enhanced angiogenesis in vivo. 4 These results indicate that saponin stimulates tube formation mainly by modifying the balance of protease/protease inhibitor secretion from HUVEC and enhancing the migration of HUVEC, and that it is effective in vivo.

Modulating Angiogenesis

“…4 The activity of ginseng extract has been studied extensively. Ambiguously, ginseng extract has been reported to promote wound healing 5 and inhibit tumor growth 6,7 through opposing effects on angiogenesis. To elucidate this perplexity in the reported effects of ginseng, we merged a chemical fingerprinting approach with a deconstructional study of the angiogenic process and identified for the first time the existence of active principles in the extract that can exert opposing effects on the final phenotype.…”

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

“…8,9) 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. 10,11) 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 11) and inhibit tumor growth 12) through opposing effects on angiogenesis.…”

Parenteral administration of GnRH constructs and adjuvants: Immune responses and effects on reproductive tissues of male mice

“…This variable response could indicate that the administered dose was sub-optimal or that male Balb/c mice are less sensitive to this vaccine compared to other mammals in which it has been tested [38]. In our studies, animals injected with ISCOMs formulations showed an enlarged spleen, an effect which could be due to the presence of a saponin component; some saponin adjuvants are known to possess an angiogenic effect and the spleen enlargement may thus be caused by increased blood supply [39,40].…”