Effects of ginsenoside Rg1 on the senescence of vascular smooth muscle cells

Abstract

ABSTRACT. The development of age-related cardiovascular disease is associated with the senescence of vascular cells. This study aimed to investigate the effect of ginsenoside Rg1 on vascular smooth muscle cell (VSMC) senescence. Primary VSMCs were cultured and divided into control, D-galactose (D-gal), Rg1-L, and Rg1-H groups, which were cultured without and with D-gal, and with low-and highconcentrations of Rg1, respectively. D-gal-induced cellular senescence was identified by b-galactosidase staining, and ultrastructural changes within the cells were observed. The expression of p16, p21, and p53 in the four groups of VSMCs was determined by western blotting, and the cell cycle was investigated by flow cytometry. Compared with the control group, there was an obvious change in the ultrastructure of VSMCs in the D-gal group, and the proportion of b-galactosidasepositive cells was significantly increased (P < 0.05). In addition, p16, p21, and p53 expression was significantly increased (P < 0.05) and the cell cycle was arrested in the G0/G1 phase. Compared with the D-gal group, the percentage of positive cells was significantly reduced (P < 0.05) in the Rg1 groups, the expression of p16, p21, and p53 was significantly reduced (P < 0.05), and the number of cells in the G0/G1 phase decreased (P < 0.05). Ginsenoside Rg1 can inhibit VSMC senescence, and the mechanisms may be related to its partial inhibition of the p16 INK4a /Rb and p53-p21Cip1/Waf1 signaling pathways during the cell cycle.

Ginsenoside Rg1 supplementation clears senescence-associated β-galactosidase in exercising human skeletal muscle

“…In this study, the results on induced SA-β-gal clearance, reversed apoptosis number, and enhanced exercise-induced iNOS mRNA and IL-6 mRNA suggest an enhanced phagocytic function of macrophage after Rg1 supplementation. This human data agreed with previous in vitro studies demonstrating an activated phagocytosis of macrophage by Rg1, mediated via nitric oxide–dependent mechanism for senescent cell clearance [7], [21].…”

“…About 20% improvement in cycling time at high intensity (80% VO 2max ) was observed after two doses of Rg1 supplementation before exercise challenge [6]. Recently, Rg1 has also been shown to decrease cell senescence in vitro [7], [8]. Accumulation of senescent cells in adult tissues implicates functional decay in adults [9].…”

“…Among the ginsenoside components of P. ginseng , Rg1 is a component that mediates the macrophage activation [21]. This component has been shown to eliminate senescent cells in vitro [7], [8]. In the present study, the changes of SA-β-gal signal, apoptotic DNA content, and CD68 + macrophage in human skeletal muscle after aerobic cycling were examined under Rg1-supplemented condition.…”

Functional roles and mechanisms of ginsenosides from Panax ginseng in atherosclerosis

“…Ginsenoside Rg1 can enhance the autophagy-related protein expression of macrophages and reduce the expression of apoptotic protein through the AMPK/mTOR pathway, thereby reducing macrophages apoptosis and enhancing autophagy [ 70 ], which helps maintain macrophages function in advanced atherosclerosis and protect lesions [ 71 ]. Besides, Rg1 can also inhibit VSMCs senescence as well as vascular intimal hyperplasia via suppressing VSMC proliferation [ 72 , 73 ].…”

Therapeutic Potential and Cellular Mechanisms of Panax Notoginseng on Prevention of Aging and Cell Senescence-Associated Diseases

“…Ginsenoside Rg1 can inhibit D-galactose-induced VSMCs senescence, and the mechanisms may be related to its partial inhibition of the p16INK4a/Rb and p53-p21Cip1/Waf1 signaling pathways during the cell cycle [ 58 ].…”