Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3

• DOI: 10.1038/ncomms7656
• Publication Date: 2015-04-14T14:55:45Z
• Authors: Vinodkumar B. Pillai; Sadhana Samant; Nagalingam R. Sun...; Hariharasundaram ...; Gene Kim; Michael Y. Bonner; Jack L. Arbiser; Douglas I. Walker; Dean P. Jones; David Gius; Mahesh P. Gupta
• Keywords: SIRT3; Honokiol

Honokiol (HKL) is a natural biphenolic compound derived from the bark of magnolia trees with anti-inflammatory, anti-oxidative, anti-tumour and neuroprotective properties. Here we show that HKL blocks agonist-induced pressure overload-mediated, cardiac hypertrophic responses, ameliorates pre-existing hypertrophy, in mice. Our data suggest anti-hypertrophic effects depend on activation deacetylase Sirt3. We demonstrate present mitochondria, enhances Sirt3 expression nearly twofold may bind to further increase its activity. Increased activity associated reduced acetylation mitochondrial substrates, MnSOD oligomycin-sensitivity conferring protein (OSCP). HKL-treatment increases rate oxygen consumption reduces ROS synthesis wild type, but not Sirt3-KO cells. Moreover, fibroblast proliferation differentiation myofibroblasts Sirt3-dependent manner. These results pharmacological activator capable blocking, even reversing, response. The chemical honokiol found trees, which are used for traditional medicine Asian countries. Here, Pillai et al, protects heart remodelling mice, reverses established by activating