Ginsenoside Rh2 Attenuates Post-Myocardial Infarction Heart Failure by Modulating the TGF-β/Smad2 Signaling Pathway

Myocardial fibrosis and oxidative stress are key drivers of post-myocardial infarction heart failure (post-MI HF). Ginsenoside Rh2 (GRh2) has shown cardioprotective potential, but its role in post-MI HF and the underlying mechanism remain unclear.

Mice with permanent left anterior descending artery ligation were treated with GRh2 (10 mg/kg/day, gavage) or enalapril for 28 days, cardiac function (echocardiography), fibrosis (histology/immunohistochemistry) and cardiac injury markers were assessed. Cardiac transcriptomes were sequenced to identify enriched pathways. H9C2 cardiomyoblasts and human iPSC-derived cardiac organoids were subjected to oxygen glucose deprivation (OGD) and treated with GRh2 with or without the TGF-β receptor agonist SRI-011381 (SRI), viability, oxidative stress, apoptosis, fibrosis and TGF-β/Smad2 signalling were measured.

In vivo, GRh2 treatment markedly improved cardiac function and reduced myocardial fibrosis in mice with post-MI heart failure. Transcriptomic analysis revealed that the TGF-β signaling pathway was substantially enriched. In vitro, GRh2 treatment significantly improved cell viability and reduced oxidative stress and fibrosis in OGD-exposed H9C2 cardiomyocytes and cardiac organoids. These protective effects were strongly associated with the suppression of the TGF-β/Smad2 signaling pathway.

GRh2 can improve myocardial function and alleviate fibrosis, oxidative stress and cell apoptosis after MI. In cells and organoids, these protective effects depend on the inhibition of the TGF-β/Smad2 signaling pathway, suggesting that this pathway is a potential mediator of the cardiac protective effect of GRh2.