Bisdemethoxycurcumin alleviates myocardial ischemia/reperfusion injury by AMPK-mediated autophagy activation and apoptosis suppression

Myocardial ischemia/reperfusion (I/R) injury impairs the prognosis of patients with cardiovascular disease. Reperfusion induces cardiomyocyte apoptosis and dysregulates autophagy, thereby disrupting cellular homeostasis and exacerbating myocardial injury. Bisdemethoxycurcumin (BDMC), a major active component of Curcumae sp., has been reported to exert pleiotropic regulatory effects on inflammatory response, apoptosis and autophagy, yet its effects and mechanisms in myocardial I/R injury remain unclear. In this study, in vivo myocardial I/R models were established in Sprague-Dawley rats via left anterior descending coronary artery ligation. TTC staining, echocardiography, hematoxylin-eosin staining, serum myocardial injury marker detection and metabolomics of myocardial tissues were performed to evaluate infarct burden, cardiac function, histopathological changes and myocardial metabolic signatures. In vitro, a hypoxia/reoxygenation (H/R) injury model was established in H9c2 cells. CCK-8 assay, flow cytometry, ROS detection and JC-1 staining were conducted to assess cell viability, apoptotic rate, oxidative stress and ΔΨm, respectively. Western blotting was performed to assess signaling proteins in both models. The results showed that BDMC markedly reduced infarct size, preserved systolic function, attenuated tissue injury and corrected I/R-induced metabolic dysfunction, notably lowering D-fructose 6-phosphate and guanosine 5'-diphosphate accumulation. In vitro, BDMC enhanced H/R-injured H9c2 cell viability, suppressed apoptosis and promoted protective autophagy. Mechanistically, BDMC upregulated p-AMPK, inhibited mTOR and HMGB1/NF-κB signaling; these effects were abrogated by Compound C, with HMGB1 silencing partially altering its anti-apoptotic effects. In conclusion, BDMC could ameliorate myocardial I/R injury in rats, with its mechanism related to AMPK activation and subsequent mTOR inhibition to promote autophagy and inhibit HMGB1/NF-κB-mediated apoptosis.