6-Gingerol Protects Against Hypertrophic Cardiomyopathy in High-Fat Diet/Low-Dose Streptozotocin-Induced Diabetic Rats

Background and objectives: Diabetes mellitus (DM)-induced hypertrophic cardiomyopathy (HCM) is the main reason for the high morbidity rate. 6-Gingerol has been shown to alleviate HCM by reducing oxidative stress and inflammation. The present study investigated its underlying mechanism, focusing on the activation of the AMPK/PGC-1a/SIRT1 pathway, aiming to reveal its therapeutic potential. Methods: Male Sprague-Dawley rats were given a high-fat diet and high fructose drink for 16 weeks and a low dose single injection of streptozotocin (22 mg/kg i.p) for DM induction. At week 8, diabetic rats were given 6-gingerol at doses of 50, 100, and 200 mg/kgBW/day for 8 weeks. Histological analysis was applied to assess cardiac structure. Western blotting was applied to assess the protein expression of AMPK/PGC-1a/SIRT1 and ELISA was used to assess the insulin signaling pathways, glutathione peroxidase (GPx), tumor necrosis factor (TNF)-a, and cardiac troponin I (cTnI). Malondialdehyde (MDA) and creatine kinase MB (CK-MB) levels were checked using colorimetric method. Results: We showed that 6-gingerol at the dose of 200 mg/kg/day alleviated HCM in diabetic rats and also enhanced the protein expression of AMPK/PGC-1a/SIRT1 and insulin signaling pathways while it decreased the levels of cTnI and CK-MB. It also increased antioxidative capacity proved by increased activity of GPx and decreased MDA and TNF-a levels. Conclusion: These findings suggest that giving 6-gingerol to the rats in doses of 50, 100, and 200 mg/kg/day may reduce DM-induced HCM, partly by activating the AMPK/PGC-1a/SIRT1 and insulin signaling pathways.