This study investigates the anti-angiogenic effect of 3 beta,12 beta, 20(S)-trihydroxy dammarane-3-O-beta-D-glucopyranosyl(1-2)-beta-D-glucopyranoside(HRG), a new chemical compound obtained by structure modification on Ginseng saponins Rg3, associated with the regulation of matrix metalloproteinases(MMPs) and its upstream signal-regulated molecule of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b-FGF) in vitro, which plays an critical role in angiogenesis during the process of carcinoma. In our study, to investigate the anti-angiogenesis effect of HRG in HUVECs, we utilized cell proliferation assay, tube formation assay, wound-healing assay, Semi-quantitative reverse transcription PCR, and Western blot assay. Our results demonstrated that HRG plays a major role in the regulation of proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGF and b-FGF in both transcriptional and post-transcriptional levels. In addition, the expression of MMP-2 and MMP-9, which were related to the ECM degradation, were down-regulated after administration of HRG as well. Overall, our results revealed that HRG strongly inhibited the process of angiogenesis and shows better effectiveness than Rg3. (C) 2017 Elsevier Inc. All rights reserved.