Vitamin B6 attenuates diabetic cardiomyopathy by targeting CtBP1 and alleviating Golgi stress via the AKT/HO-1 signaling pathway.

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes, characterized by the impairment of cardiac structure and function. Increasing evidence suggests that Golgi stress responses are involved in the pathogenesis of DCM. This study investigated the protective effects of vitamin B6 on DCM and explored the potential involvement of Golgi stress responses and the AKT/HO-1 signaling pathway in vitamin B6-mediated cardioprotection. Network pharmacology and molecular docking were used to identify potential targets of vitamin B6. A DCM mouse model was established in C57BL/6 mice using a high-fat diet and streptozotocin, and high-glucose-treated H9c2 cells were used in vitro. Cardiac function was assessed by echocardiography, histopathological changes were evaluated by HE and Masson staining, Golgi morphology was examined by transmission electron microscopy, and the expression of CtBP1, GM130, HO-1, NHE1, and P-AKT was analyzed by immunohistochemistry, immunofluorescence, and Western blotting. DCM mice exhibited increased heart weight-to-body weight ratio (HW/BW), reduced ejection fraction and fractional shortening, disordered myocardial fibers, and marked fibrosis, whereas vitamin B6 treatment significantly improved cardiac function and alleviated myocardial injury and fibrosis. Ultrastructural analysis showed Golgi fragmentation, filamentous disruption, and mitochondrial damage in DCM cardiomyocytes, all of which were ameliorated by vitamin B6. At the molecular level, DCM decreased CtBP1, GM130, HO-1, and P-AKT expression while increasing NHE1, and these changes were reversed by vitamin B6. These findings indicate that vitamin B6 may attenuate DCM through CtBP1-associated regulation and preservation of Golgi homeostasis, highlighting its potential therapeutic value.