Sulforaphane attenuates high-fat diet-induced myocardial injury via AMPK/SIRT1/P65 signaling in mice

Background: Obesity-induced metabolic disorders are closely associated with myocardial injury, in which lipid accumulation and chronic inflammation play critical roles. Activation of the AMPK/SIRT1 pathway has been reported to suppress NF-?B–mediated inflammatory responses and protect cardiac function. Sulforaphane (SFN), a bioactive isothiocyanate derived from cruciferous vegetables, exhibits potent metabolic and anti-inflammatory properties; however, its protective effects and underlying mechanisms in obesity-related myocardial injury remain incompletely understood. Objectives: This study aimed to investigate whether SFN alleviates high-fat diet (HFD)–induced myocardial injury and to elucidate the involvement of the AMPK/SIRT1/NF-?B signaling pathway. Methods: Male C57BL/6 mice were fed a normal diet or HFD, with or without SFN treatment, for 16 weeks. Metabolic parameters, serum lipid profiles, myocardial injury markers, inflammatory cytokines and histopathological changes were evaluated. In vitro, palmitic acid-treated H9c2 cardiomyocytes were used to assess the mechanistic role of AMPK/SIRT1 signaling, with pharmacological inhibition of AMPK. Results: SFN significantly reduced body weight, fasting glucose, serum triglycerides, total cholesterol, free fatty acids, and LDL levels in HFD-fed mice. SFN markedly attenuated myocardial structural damage and decreased serum CK, CK-MB, and cTnI levels. Inflammatory cytokines (TNF-?, IL-1?, IL-6) were suppressed at both serum and myocardial mRNA levels. Mechanistically, SFN enhanced AMPK phosphorylation and SIRT1 expression while inhibiting p65 phosphorylation. In vitro, AMPK inhibition reversed the anti-inflammatory effects of SFN. Conclusion: SFN effectively alleviates HFD-induced myocardial injury by activating the AMPK/SIRT1 pathway and suppressing NF-?B–mediated inflammation, highlighting its potential as a therapeutic agent for obesity-related cardiac injury.