Clin Exp Pharmacol Physiol. 2026 May;53(5):e70121. doi: 10.1111/1440-1681.70121.
ABSTRACT
OBJECTIVE: Acute myocardial infarction (AMI) remains the leading global cause of mortality. This study explored the mechanism by which ginsenoside Rg1 (Rg1) ameliorates cardiac function and ventricular remodelling (VR) in rats with AMI by regulating SH2 domain-containing adapter protein B1 (SH2B1).
METHODS: An AMI rat model was established by ligating the left anterior descending coronary artery. Gain- and loss-of-function experiments were conducted to explore the role of SH2B1 in mediating cardioprotective effects of Rg1. Cardiac function and VR were evaluated using echocardiography, enzyme-linked immunosorbent assay (ELISA) and histological staining. RT-qPCR and western blot were employed to analyse SH2B1 expression and molecular docking to predict the binding affinity between Rg1 and SH2B1.
RESULTS: Rg1 improved echocardiographic parameters, decreased levels of pro-inflammatory cytokines, reduced infarct size, weakened myocardial tissue cell apoptosis, diminished blue collagen fibre deposition and reduced the proportion of α-smooth muscle actin-positive cells in myocardial tissues of rats with AMI in a dose-dependent manner within a certain range. Additionally, SH2B1 mRNA and protein expression was elevated in the myocardial tissue of AMI rats and Rg1 dose-dependently reduced SH2B1 expression. A binding energy of -2.14 kcal/mol was observed between Rg1 and SH2B1, indicating a potential interaction. SH2B1 knockdown improved cardiac function and VR in rats with AMI, and SH2B1 overexpression partially counteracted the beneficial effects of Rg1 in AMI rats.
CONCLUSION: Rg1 improves cardiac function and VR in rats with AMI by down-regulating SH2B1; these effects are partially nullified by SH2B1 overexpression.
PMID:42020201 | DOI:10.1111/1440-1681.70121