Geniposide Protects Against Myocardial Infarction Injury via the Restoration in Gut Microbiota and Gut–Brain Axis

Improving gut dysbiosis and impaired gut–brain axis has been a potent therapeutic strategy for treating myocardial infarction (MI). Geniposide (GEN), a traditional Chinese medicine extract, has demonstrated substantial cardioprotective properties post-MI. Nevertheless, the effect of GEN on gut microbial, gut–brain communication, and its potential mechanism remains unclear. In this study, we initially found that GEN significantly alleviated MI-induced cardiac dysfunction from echocardiographic data and decreased myocardial fibrosis, inflammation, apoptosis and hypertrophy post-MI. Additionally, we investigated the effects of GEN on gut pathology, and observed that GEN led to a remarkable change in gut microbiota as evidenced by altering β-diversity and short-chain fatty acids (SCFAs) levels, and alleviated intestinal damage indicated by reduced inflammation and barrier permeability post-MI. Finally, our investigation into brain pathology revealed that GEN induced a remarkable inhibition in PVN inflammation and sympathetic activity following MI. Collectively, these findings imply that the cardioprotective effects of GEN against MI were mediated possibly via an improvement in the impaired gut–brain axis. Mechanically, GEN-induced increase of microbiota-derived SCFAs might be the critical factor linking gut microbiota and reduced neuroinflammation with PVN, which leads to the suppression of sympathetic activation, therefore protecting the myocardium against MI-induced damage.