Diabetic cardiomyopathy (DCM) is a serious diabetes complication marked by cardiac dysfunction and structural abnormalities. Mitochondrial dysfunction, driven by lipotoxicity and glucotoxicity, is central to DCM pathogenesis. SIRT6, a sirtuin family protein, is a potential therapeutic target due to its role in mitochondrial protection. This study explored morin, a natural flavonoid, as a SIRT6 activator to protect against palmitic acid-induced cardiomyopathy in H9c2 cells. In silico molecular docking identified morin as a potential SIRT6 activator with strong binding affinity, especially at residues ASP116 and PHE82. In vitro studies in H9c2 cardiomyoblasts confirmed morin’s protective effects against palmitic acid-induced toxicity. Morin pretreatment improved cell viability and reduced cytotoxicity. It enhanced glucose uptake, preserved mitochondrial membrane potential, and protected against mitochondrial damage. Morin also decreased reactive oxygen species (ROS), and lowered early and late apoptosis rates, showing strong anti-apoptotic effects. Additionally, morin upregulated SIRT6 and OPA1 expression, key genes for mitochondrial function and protection. These results suggest morin’s cardioprotective effects involve SIRT6 activation, mitochondrial protection, antioxidant activity, and anti-apoptotic mechanisms. By upregulating SIRT6 and OPA1, morin may counteract mitochondrial dysfunction in DCM. This study highlights morin’s therapeutic potential as a natural compound for DCM treatment, warranting further preclinical and clinical research.
Divya KP, Anuranjana PV, George KT, Baby K, Beegum F, Kanwar N, Kumar N, Nandakumar K, Kanwal A. Morin protects against palmitic acid-induced diabetic cardiomyopathy via SIRT6 activation and mitochondrial preservation. J Appl Pharm Sci. 2025. Article in Press. http://doi.org/10.7324/JAPS.2026.261812
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