Natural Compounds Targeting Profibrotic Signaling Pathways in Myocardial Fibrosis: Signaling Network Regulation and Therapeutic Potential

Myocardial fibrosis (MF) is a common pathological process in various cardiac diseases, including myocardial infarction (MI), hypertensive heart disease, and dilated cardiomyopathy. MF is characterized by excessive deposition of extracellular matrix (ECM), reduced myocardial compliance, and impaired cardiac function. This process can lead to arrhythmias and sudden cardiac death. Currently, effective and safe therapies for MF are limited. This review summarizes recent advances in the use of natural compounds to treat MF by regulating signaling pathways. Representative compounds, such as Salvianolic acid B (Sal B), Astragaloside IV (AS-IV), Pachymic acid, Resveratrol, Curcumin, Matrine, Artemisinin, and Artesunate, among others, can modulate multiple profibrotic signaling pathways. These compounds reduce profibrotic cytokines, inhibit collagen deposition, reverse myofibroblast differentiation, enhance ECM degradation, and alleviate inflammation and oxidative stress. As a result, they improve MF and regulate systemic inflammatory responses. However, comprehensive data on the pharmacokinetics, bioavailability, long-term safety, and clinical efficacy of these natural compounds are still lacking. Future studies should focus on optimizing delivery strategies and conducting rigorously designed clinical trials to support the clinical translation of these compounds for MF treatment.