Natural Products Targeting Myocardial Fibrosis: Pharmacological Basis, Molecular Mechanisms and Translational Barriers

Myocardial fibrosis (MF) is a hallmark of pathological cardiac remodeling, driven by extracellular matrix (ECM) accumulation, fibroblast activation, and oxidative stress. Diverse natural products—notably alkaloids, flavonoids, terpenoids, and saponins—exhibit emerging antifibrotic potential. A comprehensive literature synthesis through July 2026 across PubMed, Web of Science, and Scopus categorized these agents by phytochemical class and disease models, delineating direct antifibrotic efficacy from indirect cardioprotection. Mechanistically, these compounds target TGF-β signaling, endothelial-to-mesenchymal transition (EndMT), autophagy/mitophagy, and ECM turnover. Robust preclinical evidence correlates with integrated histopathological assessment, specifically collagen and α-SMA quantification. However, translation remains impeded by model limitations, inadequate phytochemical standardization, and a critical paucity of clinical trials. Currently, no natural product holds clinical approval for MF. Future directives necessitate rigorous botanical authentication, pharmacokinetic/pharmacodynamic profiling, and adoption of human-relevant models, such as induced pluripotent stem cell-derived cardiomyocytes, to bridge the bench-to-bedside gap.