Cinnamomum migao H.W. Li Ethanol-Water Extract Suppresses IL-6 Production in Cardiac Fibroblasts: Mechanisms Elucidated via UPLC-Q-TOF-MS, Network Pharmacology, and Experimental Assays

This study aims to elucidate the active components and underlying molecular mechanisms by which the ethanol-water extract of Cinnamomum migao H.W. Li (MG-EWE) inhibits cardiac fibroblast (CF) transdifferentiation and IL-6 production, providing insights into its anti-myocardial fibrosis effects. The chemical composition of MG-EWE was characterized using UPLC-Q-TOF-MS. Network pharmacology analysis identified active constituents and their mechanisms in inhibiting IL-6 production in CFs. An isoproterenol (ISO)-induced rat CF model was established to evaluate the effects of MG-EWE and its main monomers, Laurolitsine and Hecogenin, on cell proliferation, migration, collagen metabolism, IL-6 production, and key proteins in the ADRB2/JNK signaling pathway. A total of 173 compounds were identified in MG-EWE, with 14 core constituents regulating IL-6 synthesis via 16 key targets, including ADRB2 and MAPK9. Gene Ontology enrichment indicated that MG-EWE affects phosphorylation and the JNK signaling cascade. Molecular docking showed strong binding affinities between Laurolitsine, Hecogenin, and their targets ADRB2 and JNK. Experimentally, MG-EWE, Laurolitsine, and Hecogenin significantly inhibited ISO-induced CF proliferation, migration, and hydroxyproline synthesis, as well as the expression of p-ADRB2, p-JNK, p-c-Jun, and IL-6. MG-EWE inhibits CF transdifferentiation and IL-6 production via the ADRB2/JNK/c-Jun signaling axis, mediated by its constituents Laurolitsine and Hecogenin, highlighting its potential for drug development targeting myocardial fibrosis.