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
- 1State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China
- 2Department of Geriatrics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China
- 3Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Chronic Heart Failure, Guangdong Clinical Research Institute of Traditional Chinese Medicine, Guangzhou, 510405, People’s Republic of China
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/Mφs).
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/Mφs. 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/Mφs toward anti-inflammatory Ly6Clow phenotype (with upregulated CD206 and Arg1), suppressed pro-inflammatory Ly6Chigh 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.
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BibTeX
@article{zhao2026mechanism,
title = {{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}},
author = {Tingyao Zhao and Huili Liao and Rongfei Wang and Bodi Xiao and Zhaocong Li and Fangyuan Qu and Minqi Lu and Zhongqi Yang and Shihao Ni and Xinting Wang},
journal = {Drug Design, Development and Therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s651891},
url = {https://doi.org/10.2147/dddt.s651891},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Tingyao Zhao
AU - Huili Liao
AU - Rongfei Wang
AU - Bodi Xiao
AU - Zhaocong Li
AU - Fangyuan Qu
AU - Minqi Lu
AU - Zhongqi Yang
AU - Shihao Ni
AU - Xinting Wang
PY - 2026
DA - 2026/10/27
JO - Drug Design, Development and Therapy
DO - 10.2147/dddt.s651891
UR - https://doi.org/10.2147/dddt.s651891
AB - 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/Mφs). 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/Mφs. 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/Mφs toward anti-inflammatory Ly6Clow phenotype (with upregulated CD206 and Arg1), suppressed pro-inflammatory Ly6Chigh 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.
SN - 1177-8881
ER -