Research progress of bioactive compounds of Traditional Chinese medicine in the treatment of myocardial fibrosis-related signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis (MF),characterized by excessive extracellular matrix (ECM) remodeling,represents a central pathological process in progressive cardiovascular diseases and drives cardiac functional impairment.Contemporary anti-fibrotic therapies face limitations due to inadequate target specificity and systemic toxicity, whereas bioactive compounds derived from traditional Chinese medicine (TCM) offer novel multi-target therapeutic strategies for MF reversal. AIM OF THE STUDY: This review synthesizes evidence on molecular mechanisms by which TCM compounds modulate fibrotic signaling networks,providing translational insights for precision anti-fibrotic interventions. MATERIALS AND METHODS: Following PRISMA guidelines,we systematically searched major scientific databases (PubMed, Web of Science, Embase,Cochrane Library,CNKI) from January 2000 to September 2025 using predefined keywords: myocardial fibrosis, traditional Chinese medicine, bioactive compounds, and herbal pharma cology. Eligible experimental studies elucidating mechanistic pathways were analyzed to map chemical constituents, pharmacological actions, and pathway interactions. RESULTS: TCM-derived compounds including tanshinone IIA and astragaloside IV demonstrate anti-MF efficacy by suppressing fibroblast activation and collagen deposition through coordinated modulation of TGF-β1/Smad, MAPK, and NF-κB pathways, correlating with reduced MF severity and improved cardiac function. CONCLUSION: TCM bioactives exhibit unique therapeutic potential by remodeling the fibrotic microenvironment through multi-modal signaling pathways, overcoming limitations of single-target approaches.Current constraints include insufficient validation in dynamic disease models and interspecies pharmacokinetic variability.Future research should prioritize integrating organ-on-a-chip systems with spatial metabolomics. To bridge current translational gaps, future studies must converge cutting-edge technologies: (1) Organ-on-a-chip platforms simulating human cardiac microenvironments; (2) Spatial metabolomics mapping compound distribution; and (3) AI-driven screening to construct predictive compound-pathway-phenotype networks. Such integration, aligned with ICH guidelines, could propel TCM from empirical practice to precision cardiology.