Ginsenoside Rb1 Improves Atherosclerosis by Inhibiting Endothelial Cell Pyroptosis

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pharmacology

Background:

• Atherosclerosis (AS) is a chronic inflammatory disease characterized by plaque buildup in arteries.
• Endothelial cell (EC) pyroptosis, a pro-inflammatory form of cell death, plays a critical role in AS pathogenesis.
• Ginsenoside Rb1 (Gs-Rb1), a major active component of ginseng, has shown potential anti-inflammatory and antioxidant properties.

Purpose of the Study:

• To investigate the therapeutic effects of Gs-Rb1 on EC pyroptosis in an AS model.
• To elucidate the underlying mechanisms of Gs-Rb1's anti-atherosclerotic action.

Main Methods:

• An in vivo AS model was established in ApoE-/- mice fed a high-fat diet, treated with Gs-Rb1.
• In vitro experiments utilized mouse aortic endothelial cells (MAECs) stimulated with oxidized low-density lipoprotein (ox-LDL) and treated with Gs-Rb1.
• Pathological changes, pyroptosis markers (caspase-1, GSDMD, NLRP3), inflammatory cytokines (IL-18, IL-1β), and cell death were assessed using HE staining, Oil Red O, immunofluorescence, Western blotting, RT-PCR, ELISA, and flow cytometry.

Main Results:

• Gs-Rb1 significantly reduced aortic plaque area and atherosclerotic lesion severity in vivo.
• Gs-Rb1 treatment decreased the expression of pyroptosis-related proteins and mRNA in aortic tissues.
• In vitro, Gs-Rb1 inhibited ox-LDL-induced EC pyroptosis and reduced cell death rates.

Conclusions:

• Gs-Rb1 exhibits significant therapeutic effects against atherosclerosis at both animal and cellular levels.
• Inhibition of endothelial cell pyroptosis is identified as a key mechanism for Gs-Rb1's anti-atherosclerotic activity.
• Gs-Rb1 represents a promising therapeutic agent for managing atherosclerosis.