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Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti‑obesity and anti‑inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin‑1 (SIRT1) was activated by Rb1 to protect HUVECs from H2O2‑induced senescence. However, the mechanisms are not fully understood. The present study examined the role of AMP‑activated protein kinase (AMPK), an energy sensor of cellular metabolism, in the signaling pathway of SIRT1 during H2O2‑stimulated HUVEC aging. It was identified that Rb1 restored the H2O2‑induced reduction of SIRT1 expression, which was consistent with our previous study, together with the activation of AMPK phosphorylation. Using compound C, an AMPK inhibitor, the role of AMPK in the protective effect of Rb1 against H2O2‑induced HUVEC senescence was examined. It was identified that the induction of phosphorylated AMPK by Rb1 markedly increased endothelial nitric oxide synthase expression and nitric oxide production, and suppressed PAI‑1 expression, which were abrogated in HUVECs pretreated with compound C. Further experiments demonstrated that nicotinamide, a SIRT1 inhibitor, downregulated the phosphorylation of AMPK and reduced the protective effects of Rb1 against H2O2‑induced endothelial aging. Taken together, these results provide new insights into the possible molecular mechanisms by which Rb1 protects against H2O2‑induced HUVEC senescence via the SIRT1/AMPK pathway.

Oxidative low-density lipoprotein (ox-LDL) induces endothelium senescence and promotes atherosclerosis. Ginsenoside Rb1 (gRb1) has been proved to protect human umbilical vein cells (HUVECs), but its effect on ox-LDL-induced endothelium senescence and the underlying mechanism remains unknown. This study is to explore the involvement of the SIRT1/Beclin-1/autophagy axis in the effect of gRb1 on protecting endothelium against ox-LDL-induced senescence. Hyperlipidemia of Sprague Dawley rats was induced by high-fat diet, and gRb1 was intraperitoneal injected. A senescence model of HUVECs induced by ox-LDL was also established. The results showed that gRb1 alleviated hyperlipidemia-induced endothelium senescence and ox-LDL-induced HUVECs senescence. GRb1 also restored the reductions in SIRT1 and autophagy, which were involved in the anti-senescence effects. Beclin-1 acetylation was reduced, and the correlation between SIRT1 and Beclin-1 was increased by gRb1. Results of our study demonstrated the anti-senescence function of gRb1 against hyperlipidemia in the endothelium, and the underlying mechanism involves the SIRT1/Beclin-1/autophagy axis.

Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti-obesity and anti-inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin-1 (SIRT1) was activated by Rb1 to protect HUVECs from H2O2-induced senescence. However, the mechanisms are not fully understood. The present study examined the role of AMP-activated protein kinase (AMPK), an energy sensor of cellular metabolism, in the signaling pathway of SIRT1 during H2O2-stimulated HUVEC aging. It was identified that Rb1 restored the H2O2-induced reduction of SIRT1 expression, which was consistent with our previous study, together with the activation of AMPK phosphorylation. Using compound C, an AMPK inhibitor, the role of AMPK in the protective effect of Rb1 against H2O2-induced HUVEC senescence was examined. It was identified that the induction of phosphorylated AMPK by Rb1 markedly increased endothelial nitric oxide synthase expression and nitric oxide production, and suppressed PAI-1 expression, which were abrogated in HUVECs pretreated with compound C. Further experiments demonstrated that nicotinamide, a SIRT1 inhibitor, downregulated the phosphorylation of AMPK and reduced the protective effects of Rb1 against H2O2-induced endothelial aging. Taken together, these results provide new insights into the possible molecular mechanisms by which Rb1 protects against H2O2-induced HUVEC senescence via the SIRT1/AMPK pathway. [ABSTRACT FROM AUTHOR]

Purposes: We have previously reported that Ginsenoside Rb1 may effectively prevent HUVECs from senescence, however, the detailed mechanism has not demonstrated up to now. Recent studies have shown that sirtuin-1 (Sirt1) plays an important role in the development of endothelial senescence. The purpose of this study was to explore whether Sirt1 is involved in the action of Ginsenoside Rb1 regarding protection against H2O2-induced HUVEC Senescence. Methods and Results: Senescence induced by hydrogen peroxide (H2O2) in human umbilical vein endothelial cells (HUVECs) was examined by analyzing plasminogen activator inhibitor-1 (PAI-1) expression, cell morphology, and senescence-associated beta-galactosidase (SA-β-gal) activity. The results revealed that 42% of control-treated HUVECs were SA-β-gal positive after treatment by 60 µmol/L H2O2, however, this particular effect of H2O2 was decreased more than 2-fold (19%) in the HUVECs when pretreated with Rb1 (20 µmol/L) for 30 min. Additionally, Rb1 decreased eNOS acetylation, as well as promoted more NO production that was accompanied by an increase in Sirt1 expression. Furthermore, upon knocking down Sirt1, the effect of Rb1 on HUVEC senescence was blunted. Conclusions: The present study indicated that Ginsenoside Rb1 acts through stimulating Sirt1 in order to protect against endothelial senescence and dysfunction. As such, Sirt1 appears to be of particular importance in maintaining endothelial functions and delaying vascular aging. [ABSTRACT FROM AUTHOR]