A Natural Compound (Ginsenoside Re) Isolated from Panax ginseng as a Novel Angiogenic Agent for Tissue Regeneration

Abstract

The primary challenge for tissue engineering is to develop a vascular supply that can support the metabolic needs of the engineered tissues in an extracellular matrix. In this study, the feasibility of using a natural compound, ginsenoside Re, isolated from Panax ginseng in stimulating angiogenesis and for tissue regeneration was evaluated. Effects of ginsenoside Re on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were examined in vitro. Additionally, angiogenesis and tissue regeneration in a genipin-fixed porous acellular bovine pericardium (extracellular matrix; ECM) incorporated with ginsenoside Re implanted subcutaneously in a rat model were investigated. Basic fibroblast growth factor (bFGF) was used as a control. It was found that HUVEC proliferation, migration in a Transwell plate, and tube formation on Matrigel were all significantly enhanced in the presence of bFGF or ginsenoside Re. Additionally, effects of ginsenoside Re on HUVEC proliferation, migration, and tube formation were dose-dependent and reached a maximal level at a concentration of about 30 microg/ml. The in vivo results obtained at 1 week postoperatively showed that the density of neocapillaries and the tissue hemoglobin content in the ECMs were significantly enhanced by bFGF or ginsenoside Re. These results indicated that angiogenesis in the ECMs was significantly enhanced by loading with bFGF or ginsenoside Re. At 1 month postoperatively, vascularzied neo-connective-tissue fibrils were found to fill the pores in the ECMs loaded with bFGF or ginsenoside Re. The aforementioned results indicated that like bFGF, ginsenoside Re-associated induction of angiogenesis enhanced tissue regeneration, supporting the concept of therapeutic angiogenesis in tissue-engineering strategies.