Work

Mechanism Study of Ginsenoside Rd in the Prevention and Treatment of Post-Myocardial Infarction Heart Failure: Network Pharmacology Combined with in vivo and in vitro Experiments Verification

Year: 2026

Type: article

Abstract: Purpose: This study aims to investigate the immunoprotective mechanisms of GSRd, an active ingredient of Panax ginseng C.A. Mey ( P. ginseng C.A. Mey), against post-MI HF, with particular focus on its regulatory effects on regulatory T cells (Tregs) and Monocytes/macrophages (Mos/M&phis;s). Materials and Methods: UPLC-MS/MS was used to identify GSRd. A mouse post-MI HF model was established by LAD ligation to observe GSRd-mediated changes in Tregs, IL-10 and Mos/M&phis;s. Network pharmacology predicted GSRd core targets against post-MI HF. Single-cell virtual knockout evaluated target function, while protein-protein docking predicted IL-10-core target binding regions. In vitro, LPS-stimulated RAW264.7 macrophages were applied for inflammatory modeling, with exogenous IL-10 as positive control and Stattic for functional reverse validation of GSRd. Results: UPLC-MS/MS confirmed GSRd in P. ginseng C.A. Mey. GSRd ameliorated cardiac function and alleviated myocardial fibrosis in post-MI HF mice. Immunologically, GSRd facilitated the recruitment of Tregs in failing myocardium and peripheral circulation and elevated IL-10 expression. Furthermore, GSRd promoted the polarization of Mos/M&phis;s toward anti-inflammatory Ly6C low phenotype (with upregulated CD206 and Arg1), suppressed pro-inflammatory Ly6C high polarization, and reduced the secretion of TNF-ppressed pro-inflammatory Ly6Cin post-MI HF mice. Immunologically, GSRd facilitated the recruitment of Tregs in failing myocardium and peripheral ci of STAT3 in cardiac monocytes/macrophages predicted that STAT3 acts as a critical regulator maintaining cardiac inflammatory balance and immune homeostasis. Protein-protein interaction analysis predicted the binding domains between IL-10 and STAT3; molecular docking predicted that ginsenoside Rd can stably bind to Foxp3, IL-10 and STAT3. In vitro experiments revealed that GSRd promotes STAT3 phosphorylation to induce RAW264.7 macrophage polarization toward an anti-inflammatory phenotype, and Stattic attenuates the protective effects of GSRd. Conclusion: The present study demonstrates that GSRd confers therapeutic benefits against post-MI HF via modulating the cardiac immune microenvironment. Keywords: ginsenoside Rd, Panax ginseng C.A. Mey, post-myocardial infarction heart failure, regulatory T cells, monocytes/macrophages

Source: Drug Design Development and Therapy

DOI: 10.2147/dddt.s651891