Effect of Ginsenoside Rh1 on Proliferation, Apoptosis, and Oxidative Stress in Vascular Endothelial Cells by Regulation of the Nuclear Erythroid 2-related Factor-2/Heme Oxygenase-1 Signaling Pathway

Abstract

:This study aimed to investigate the role of ginsenoside Rh1 in regulating the proliferation, apoptosis, and oxidative stress in oxidized low-density lipoprotein (ox-LDL)-treated human vascular endothelial cells (VECs) and the underlying mechanisms. VECs were treated with ox-LDL to generate an in vitro atherosclerosis model. The effect of ginsenoside Rh1 on cell viability and proliferation was examined by MTT and colony formation assays, respectively, and cell apoptosis was determined by flow cytometry and transferase dUTP nick end-labeling assay. The levels of reactive oxygen species, malondialdehyde, and superoxide dismutase activity were detected using biological assays. Finally, the effect of ginsenoside Rh1 on the levels of BAX and BCL-2 and the nuclear erythroid 2-related factor-2/heme oxygenase (HO)-1 signaling pathway was determined by quantitative real-time polymerase chain reaction and western blot assays. Treatment with ginsenoside Rh1 significantly increased the proliferation and decreased the apoptosis of ox-LDL–treated VECs in a dose-dependent manner. Moreover, ginsenoside Rh1 also relieved oxidative stress in ox-LDL–treated VECs by activating the Nrf2/HO-1 signaling pathway. Thus, ginsenoside Rh1 affects the proliferation, apoptosis, and oxidative stress in ox-LDL–treated VECs by activating the Nrf2/HO-1 signaling pathway.

Saponins as therapeutic candidates for atherosclerosis

“…The aforementioned saponins may exert their anti‐apoptotic effects through the regulation of autophagy (Yan et al, 2022). In ox‐LDL‐induced VECs, ginsenoside Rh1 demonstrated a reduction in the number of Annexin V/PI‐positive cells and the percentage of TUNEL‐positive cells, along with a downregulation of Bax expression and an upregulation of Bcl‐2 expression, suggesting that the anti‐apoptotic effects of ginsenoside Rh1 are mediated through the Nrf2/HO‐1 pathway (Xu et al, 2022). Similarly, in EA.hy926 cells exposed to ox‐LDL/HG, ginsenoside Rb1 downregulates the expression of cleaved caspase‐3, and cytoplasmic Cyt‐c, attenuates mitochondrial ROS production, stabilizes mitochondrial membrane potential, thus effectively inhibiting cell apoptosis (Wang et al, 2022).…”

“…Similarly, ginsenoside Rh1 was found to alleviate ox‐LDL‐induced oxidative stress in HUVECs by activating the Nrf2/HO‐1 pathway. This activation was evidenced by a reduction in ROS and MDA levels, as well as a dose‐dependent increase in SOD activity (Xu et al, 2022). Moreover, AS‐IV exhibited a concentration‐dependent upregulation of Nrf2 and HO‐1 mRNA expression together with a decrease in ROS levels and NADPH oxidase activity in ox‐LDL‐induced HUVECs, resulting in a reduction of oxidative stress (Zhu et al, 2019).…”

Oxidative Stress and Ginsenosides: An Update on the Molecular Mechanisms

“…Liu et al [ 81 ] found that ginsenoside Rb1 can significantly increase the spinal cord function score, reduce serum MDA content, increase SOD, CAT, and GSH activity, and upregulate Nrf2/HO-1 expression in a spinal cord injury (SCI) rat model. Xu et al [ 82 ] demonstrated that ginsenoside Rh1 promotes proliferation, inhibits apoptosis, and relieves oxidative stress in oxidized low-density lipoprotein- (ox-LDL-) induced vascular endothelial cells (VECs) by activating the Nrf2/HO-1 signaling pathway. Zhang et al [ 83 ] studied the effects of ginsenoside Rg1 on SCI and found that Rg1 could significantly increase the contents of SOD and GSH and inhibit the production of MDA, the potential mechanism of which may be that it exerts antioxidant stress and anti-inflammatory effects by activating Nrf2/HO-1 signaling pathway.…”

Roles of Reactive Oxygen Species in Vascular Complications of Diabetes: Therapeutic Properties of Medicinal Plants and Food

“…Ginsenoside compound K prevented ox-LDL-induced HUVECs injury by the inhibition of NF-κB/p38/JNK pathways [141]. At the same time, these effects also involved the activation of the Nrf2/HO-1 pathway [142,143]. Even in healthy model rats, ginseng extract increased vasodilation by reducing the level of lysophosphatidylcholine (LPC) that is related to atherosclerosis-induced tissue damage [144].…”