Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax ginseng: In vitro and in vivo studies

The study was designed to investigate the stability of ginsenoside Rg1 (Rg1) and Re (Re), two natural herbal compounds isolated from Panax ginseng, based on their activity to promote angiogenesis in vitro and in vivo. After being treated at different temperatures, pHs, and solvent species for distinct durations, the remaining activities of Rg1 and Re on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation were examined in vitro. Additionally, the remaining activity of each treated test agent, mixed in a growth factor-reduced Matrigel, in stimulating angiogenesis was evaluated subcutaneously in a mouse model. Basic fibroblast growth factor (bFGF) was used as a control. It was found in vitro that HUVEC proliferation, migration in a Transwell plate, and tube formation on Matrigel were all significantly enhanced in the presence of bFGF, Rg1, or Re. However, after being treated at different temperatures, pHs, or solvent species, the remaining activity of bFGF on HUVEC behaviors reduced significantly. This observation was more significant with increasing the duration of treatment. In contrast, the activities of Rg1 and Re remained unchanged throughout the entire course of the study. The in vivo results observed on day 7 after implantation showed that the blank control (Matrigel alone) was slightly vascularized. In contrast, the density of neo-vessels in the Matrigel plug mixed with bFGF, Rg1, or Re was significantly enhanced. However, after being treated, the density of neo-vessels was significantly reduced in the Matrigel plug mixed with bFGF, while those of Rg1 and Re remained unchanged. The aforementioned results suggested that Rg1 and Re could be a novel group of nonpeptide angiogenic agents with a superior stability and may be used for the management of tissue regeneration.