Cryptotanshinone Alleviates Cardiac Hypertrophy Through SIRT3-Mediated Epigenetic Regulation and Mitochondrial Dynamics

Abstract

Cryptotanshinone (CTS), a bioactive diterpenoid extracted from Salvia miltiorrhiza Bunge, has long been recognized as a traditional Chinese herbal compound. This study reveals that CTS exerts potent anti-hypertrophic effects against angiotensin II (Ang II)-induced cardiac hypertrophy by targeting Sirtuin 3 (SIRT3)-mediated epigenetic and mitochondrial pathways. In both in vitro and in vivo models, CTS ameliorated pathological hypertrophy, oxidative stress, inflammation, and apoptosis. Mechanistically, CTS upregulated SIRT3, reducing histone H3K9 acetylation (H3K9ac) and restoring mitochondrial dynamics by balancing fission (DRP1) and fusion (MFN2) proteins. Genetic ablation of SIRT3 exacerbated hypertrophy and mitochondrial dysfunction, while pharmacological inhibition with 3-TYP abolished CTS benefits. These findings elucidate CTS as a therapeutic candidate for cardiac hypertrophy by activating SIRT3, which is accompanied by reduced H3K9ac and restored DRP1/MFN2 balance, highlighting potential in cardiac hypertrophy treatment.