Plumbagin improves myocardial fibrosis after myocardial infarction by inhibiting the AKT/mTOR pathway to upregulate autophagy levels.

Cardiac fibrosis is a chronic inflammatory response that considerably impacts cardiac function following myocardial infarction (MI). Although Plumbagin, a natural compound, has been shown to have anti-fibrotic effects by suppresses the ROS and NF-κB pathways in liver fibrosis, its role in regulating cardiac function and cardiac fibrosis post-MI remains unknown. In this study, we demonstrate that Plumbagin effectively inhibits TGF-β1-induced myocardial fibroblast fibrosis and promotes autophagy activation by suppressing the AKT/mTOR pathway. Consistent results were obtained from MI mouse model, which demonstrated that Plumbagin improved cardiac function in mice after MI, reduced the myocardial scar area, and downregulated the expression of fibrosis-related genes. These findings align with our in vitro results, as Plumbagin also inhibited AKT/mTOR activity and increased autophagy levels. Furthermore, we artificially elevated p-mTOR expression in vitro using an mTOR agonist, which reversed the therapeutic effects of Plumbagin, as evidenced by decreased autophagy levels and increased expression of fibrosis-related genes. Our results show that Plumbagin can partially reduce cardiac fibrosis by activating autophagy through modulation of the AKT/mTOR pathway.