Ginsenoside Rb1 Improves Atherosclerosis by Inhibiting Endothelial Cell Pyroptosis.

Abstract

PURPOSE: This study aimed to investigate the effect of ginsenoside Rb1 (Gs-Rb1) on endothelial cell (EC) pyroptosis in atherosclerosis (AS). METHOD: ApoEmice and mouse aortic endothelial cells (MAECs) were used as research subjects. An in vivo AS model was established by feeding ApoEmice a high-fat diet (HFD) for 3 months, followed by intragastric administration of Gs-Rb1 at 40 mg/kg/day for 3 months. Pathological changes were evaluated by hematoxylin-eosin (HE) and Oil Red O staining. Caspase-1 expression was detected by immunofluorescence. Pyroptosis-related protein and mRNA levels were measured by Western blotting and RT-PCR. Inflammatory factors (IL-18 and IL-1β) and LDH were quantified by ELISA. For in vitro experiments, MAECs were stimulated with oxidized low-density lipoprotein (ox-LDL, 150 μg/mL) to induce pyroptosis, followed by treatment with Gs-Rb1 (60 or 80 μg/mL) for 12 h. Cell death was assessed by flow cytometry. RESULT: Gs-Rb1 significantly reduced aortic plaque area in mice. It decreased the expression of pyroptosis-related proteins (caspase-1, cleaved caspase-1, GSDMD, and NLRP3) and mRNA levels in aortic tissues. Serum levels of LDH, IL-18, and IL-1β were also significantly reduced. In vitro, Gs-Rb1 reduced cell death rate and inhibited pyroptosis in endothelial cells (ECs). CONCLUSION: This study confirms the therapeutic effect of Gs-Rb1 on AS at both animal and cellular levels. Inhibition of EC pyroptosis may be the key mechanism underlying the anti-atherosclerotic effects of Gs-Rb1.