Hypertrophic cardiomyopathy (HCM) associated with diabetes mellitus (DM) contributes significantly to elevated mortality rates. Previous studies have demonstrated that 6-gingerol mitigates HCM through attenuation of oxidative stress and inflammatory responses. This research explored the mechanisms involved, with particular emphasis on the AMPK/PGC-1α/SIRT1 signaling cascade, to assess its potential as a treatment option. Male Sprague-Dawley rats were fed a high-fat diet combined with high-fructose water for 16 weeks, followed by a single low-dose intraperitoneal injection of streptozotocin (22 mg/kg) to induce diabetes. Starting from week 8, the diabetic animals received oral administration of 6-gingerol at 50, 100, or 200 mg/kg body weight daily for 8 weeks. Cardiac tissue morphology was evaluated using histopathology. Protein levels of AMPK/PGC-1α/SIRT1 were measured via Western blot analysis, while ELISA quantified components of insulin signaling, glutathione peroxidase (GPx) activity, tumor necrosis factor-α (TNF-α), and cardiac troponin I (cTnI). Colorimetric assays determined malondialdehyde (MDA) and creatine kinase MB (CK-MB) concentrations. Administration of 6-gingerol at 200 mg/kg/day effectively reduced HCM features in diabetic rats, increased expression of AMPK/PGC-1α/SIRT1 proteins and insulin signaling components, and lowered cTnI and CK-MB concentrations. Additionally, it improved antioxidant defense by elevating GPx activity and reducing MDA and TNF-α levels. The results indicate that daily oral doses of 6-gingerol (50, 100, and 200 mg/kg) can mitigate diabetes-related HCM, potentially through enhancement of the AMPK/PGC-1α/SIRT1 axis and restoration of insulin signaling pathways.
