Myocardial ischemia/reperfusion (MI/R) injury represents a primary etiology of mortality on a global scale, presenting a critical challenge to cardiovascular well-being. Prior research indicates that Ginsenoside Rg1 exerts suppressive effects on inflammatory cascade activation, oxidative stress, and myocardial damage, implying its potential utility as a therapeutic intervention for MI/R injury. Nevertheless, the precise underlying molecular mechanisms require more comprehensive investigation. An in vivo MI/R model was established in Sprague-Dawley rats via ligation of the left anterior descending coronary artery. Myocarditis, macrophage polarization, and fibrotic changes were assessed by evaluating the organ index, electrocardiographic alterations, myocardial infarct size, histopathological variations, and the expression profiles of cardiac injury markers and pro-inflammatory mediators. Additionally, rat bone marrow-derived macrophages (BMDMs) were utilized to explore the in vitro regulatory impacts of Rg1 on absent in melanoma 2 (AIM2) inflammasome activation and macrophage phenotypic polarization. The administration of Rg1 demonstrated dose-dependent cardioprotective properties and substantially mitigated MI/R-induced damage. Rg1 markedly suppressed myocardial inflammation and impeded M1 macrophage polarization during the course of MI/R injury. Moreover, Rg1 considerably decreased cardiac fibrosis secondary to MI/R insult. This anti-fibrotic activity may play a pivotal role in maintaining myocardial structural integrity and ventricular function post-ischemia. Concurrently, Rg1 efficiently obstructed the activation of the AIM2 inflammasome in vitro, emphasizing its capability to serve as a critical modulator of inflammatory signaling pathways. The present study clarifies the diverse mechanisms mediating the cardioprotective efficacy of Rg1, specifically demonstrating its capacity to alleviate inflammatory responses, modulate macrophage polarization states, and suppress fibrotic progression.
