Musk attenuates experimental myocardial injury by reducing TLR2/MYD88-related signaling and PANoptosis-associated markers.

OBJECTIVES: Musk has traditionally been used for cardiovascular disorders, but its active constituents and mechanisms of action in acute myocardial infarction (AMI) remain unclear. METHODS: Musk constituents were profiled by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS). Network pharmacology and pathway enrichment were performed by intersecting compound targets with AMI-related genes. Predictions were validated via permanent left anterior descending-ligated rat AMI models and isoproterenol-damaged H9C2 cardiomyocytes. Indicators including cardiac function, histology, myocardial injury biomarkers, mitochondrial membrane potential, inflammation and pathway proteins were detected. KEY FINDINGS: Among the 106 identified compounds, 98 had valid PubChem CIDs, and 95 were associated with 715 unique targets. A total of 180 overlapping AMI-relevant targets were screened, with five literature-supported inflammatory cell death targets supplemented after annotation and deduplication. Seventeen constituents modulated six Toll-like Receptors (TLR) pathway genes: TLR4, NFKB1, TNF, IL6, CXCL8, and MAPK14. In vivo, musk pretreatment preserved cardiac function, reduced infarct size and myocardial injury biomarkers, and alleviated myocardial structural damage. In vitro, it elevated H9C2 viability, stabilized mitochondrial membrane potential, inhibited inflammatory release and suppressed apoptosis, pyroptosis, and necroptosis. CONCLUSIONS: Musk pretreatment attenuated experimental myocardial injury, and these effects were associated with reduced TLR2-MYD88-related signaling and lower levels of PANoptosis-associated markers.