Ginsenoside Rb1 blocks Homocysteine-induced endothelial dysfunction

Abstract

Background. Homocysteine (HCY) is an independent risk factor for atherosclerosis. This study is to investigate the effect of ginsenoside Rb1, a major constituent of ginseng, on HCY-induced endothelial dysfunction and molecular changes in porcine coronary arteries. Methods. Coronary arteries were harvested from pig hearts and cut into 5-mm rings, which were divided into 6 groups including control, HCY alone (50 μM), low-dosed (1 μM), or high-dose (10 μM) Rb1 alone, and HCY plus low-dose or high-dose Rb1. After 24 h incubation, the rings were analyzed for vasomotor function in response to U46619, bradykinin, and sodium nitroprusside (SNP), respectively. In addition, superoxide anion was assessed by lucigenin-enhanced chemiluminescence analysis. Endothelial nitric oxide synthase (eNOS) expression was studied by real-time RT-PCR and Western blot. Results. Endothelium-dependent relaxation (bradykinin) was significantly reduced in rings treated with HCY alone as compared to the control (49.80% versus 71.77%, n = 8, P < 0.05), while either high-dose or low-dose Rb1 alone did not affect endothelium-dependent relaxation. Low-dose Rb1-HCY combined group had partially improved endothelium-dependent relaxation (54.44%), while high-dose Rb1-HCY combined group showed complete recovery of endothelium-dependent relaxation (72.89%). There was no substantial difference in maximal contraction induced by U46619 or endothelium-independent relaxation by SNP among all groups ( P > 0.05). Moreover, superoxide anion was markedly increased by 137% in HCY-treated group as compared to the control, but there was no significant changes from the control in all other groups ( P > 0.05). Last, eNOS mRNA and protein levels were substantially reduced in HCY-treated group, but not in Rb1-HCY combined groups. Conclusions. This is the first study to demonstrate that ginsenoside Rb1 can effectively block HCY-induced endothelial dysfunction and superoxide anion production as well as eNOS down regulation in porcine coronary arteries. This study suggests that ginseng and its active constituents may have potential clinical applications in controlling HCY-associated vascular injuries.