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

• Published in: British journal of pharmacology Vol. 115; no. 7; pp. 1188 - 1193
• Main Authors: Morisaki, Nobuhiro, Watanabe, Satoe, Tezuka, Mariko, Zenibayashi, Mika, Shüna, Ritsuko, Koyama, Noriyuki, Kanzaki, Tetsuto, Saito, Yasushi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-1995; Nature Publishing
• Subjects: angiogenesis; Animals; Biological and medical sciences; Cell Division - drug effects; Cell Line; Cell Movement - drug effects; Culture Media, Conditioned; endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Ginseng; Humans; Male; Medical sciences; migration; Neovascularization, Physiologic - drug effects; Panax - chemistry; Pharmacology. Drug treatments; Plants, Medicinal; Plasminogen Activator Inhibitor 1 - metabolism; plasminogen activator inhibitor‐1; proliferation; Rats; Rats, Wistar; saponin; Saponins - pharmacology; Skin, nail, hair, dermoskeleton; Tissue Plasminogen Activator - pharmacology; tissue‐type plasminogen activator; Umbilical Veins; wound healing; Wound Healing - drug effects; Endocrinopathy; Human; Cell culture; Skin disease; Endothelial cell; Diabetes mellitus; Trauma; In vitro; Wound; Saponin; Angiogenesis; In vivo; Local administration; Healing agent; Animal; Plant origin; Complication; Ginseng; Mechanism of action
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1995.tb15023.x

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‐1 (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 μg ml−1significantly 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 44μg ml−1 of saponin, but then was significantly decreased at 50 and 100 μg ml−1. Cell proliferation was only slightly enhanced by 1–100 μg ml−1 of saponin, but migration was significantly enhanced by 10–100 μg ml−1 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.