Ginsenoside Rh2 Ameliorates Myocardial Infarction by Regulating Cardiomyocyte Pyroptosis Based on Network Pharmacology, Molecular Docking, and Experimental Verification.

Abstract

Myocardial infarction (MI) is a significant threat to human health worldwide. Following MI, cardiomyocytes (CMs) undergo pyroptosis, exacerbating the damage caused by infarction. Ginseng may play a role in alleviating CM pyroptosis. However, further exploration is needed regarding its main active ingredients and effects. By employing network pharmacology on the active ingredients of ginseng, MI and pyroptosis, and employing molecular docking between such ingredients and pyroptosis-related proteins, we screened for the main ingredient of ginseng. Through network pharmacology and molecular docking, we identified ginsenoside Rh2, which acts on MI and cell pyroptosis, as the most likely active ingredient that stably binds to pyroptosis-related proteins. We subsequently constructed a neonatal rat CM oxygen-glucose deprivation (OGD) model in vitro and an MI mouse model in vivo. Ginsenoside Rh2 was administered, with losartan used as a positive control. In the in vitro OGD model, ginsenoside Rh2 increased the viability of primary rat CMs and mitigated OGD-induced pyroptosis. In the in vivo MI model, ginsenoside Rh2 reduced CM pyroptosis, decreased infarct size, and subsequently improved cardiac function. Our study provides a novel therapeutic strategy for MI by attenuating CM pyroptosis.