Elucidation of the mechanisms underlying the angiogenic effects of ginsenoside Rg₁ in vivo and in vitro

The major active constituents of ginseng are ginsenosides, and Rg ₁ is a predominant compound of the total extract. Recent studies have demonstrated that Rg₁ can promote angiogenesis in vivo and in vitro. In this study, we used a DNA microarray technology to elucidate the mechanisms of action of Rg₁. We report that Rg₁ induces the proliferation of HUVECs, monitored using [³H]-thymidine incorporation and Trypan blue exclusion assays. Furthermore, Rg₁ (150-600 nM) also showed an enhanced tube forming inducing effect on the HUVEC. Rg₁ was also demonstrated to promote angiogenesis in an in vivo Matrigel plug assay, and increase endothelial sprouting in the ex vivo rat aorta ring assay. Differential gene expression profile of HUVEC following treatment with Rg ₁ revealed the expression of genes related to cell adhesion, migration and cytoskeleton, including RhoA, RhoB, IQGAP1, CALM2, Vav2 and LAMA4. Our results suggest that Rg₁ can promote angiogenesis in multiple models, and this effect is partly due to the modulation of genes that are involved in the cytoskeletal dynamics, cell-cell adhesion and migration.