Muscone Inhibits Angiotensin II–induced Cardiac Hypertrophy Through the STAT3, MAPK and TGF-β/SMAD Signaling Pathways

Abstract

Abstract Context: Muscone is a chemical monomer derived from musk. Although many studies have confirmed the cardioprotective effects of muscone, the effects of muscone on cardiac hypertrophy and its potential mechanisms are unclear. Objective: The aim of the present study was to investigate the effect of muscone on angiotensin (Ang) II-induced cardiachypertrophy. Materials and methods: The viability of H9C2 and AC16 cells was assessed by CCK8 assay. The expression of proteins was evaluated by RT-PCR and Western blot analysis. Echocardiographic paraments were obtained by a Visual sonics high resolution Vevo 2100 system. H&E staining was used to assess myocardial structural changes. Masson trichrome staining was used to assess degree of fibrosis. Serum Biochemical Indexes were detected by automatic chemistry analyzer. Results: In the present study, we found for the first time that muscone exerted inhibitory effects on Ang II-induced cardiac hypertrophy and cardiac injury in mice. Secondly, we showed that muscone attenuated cardiac injury by reducing the secretion of proinflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Moreover, we found that muscone exerted cardioprotective effects by inhibiting phosphorylation of key proteins in the STAT3, MAPK and TGF-β/SMAD pathways. In addition, the in vivo and in vitro validation found no significant toxicity or side effects of muscone on normal cells and organs. Discussion and conclusions: Muscone could attenuate Ang II-induced cardiac hypertrophy, in part, by inhibiting the STAT3, MAPK, and TGF-β/SMAD signaling pathways.