α-Mangostin prevents diabetic cardiomyopathy by inhibiting oxidative damage and lipotoxicity through the AKT–FOXO1–CD36 pathway

作者：Xue Bai, Ziqian Zhang, Miao Zhang, Jiaojiao Xu, Keting Dong, Qian Du, Lei Chen, Ping Ma, Jianhong Yang · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1566311 · 被引用次数：11 · 研究领域：Diet, Metabolism, and Disease、Natural Compound Pharmacology Studies、Calcium signaling and nucleotide metabolism

Introduction Diabetic cardiomyopathy (DCM), a cardiac complication of diabetes, is the main cause of the high prevalence of heart failure and associated mortality in diabetic patients. Oxidative stress and lipid metabolism disorder-induced myocardial cell damage are part of the pathogenesis of DCM. In this study, we investigated the effects of alpha-mangostin (A-MG), a natural antioxidant extracted from mangosteen peel, on in vitro and in vivo DCM models. Methods H9C2 rat cardiomyocytes were treated with high glucose (HG) and palmitic acid (PA) for 24 h to establish an in vitro DCM cell model. Cell viability and cytotoxicity were evaluated after treatment with varying concentrations of A-MG (0.3, 1, 3, 9, or 27 μM) using Cell Counting Kit-8 (CCK8) and lactate dehydrogenase (LDH) assays. Flow cytometry assessment was used to detect apoptosis. Molecular mechanisms were investigated through transcriptome analysis, quantitative PCR (RT-qPCR), and Western blotting. Type 2 diabetic (T2D) mice, induced by feeding a high-fat diet (HFD) combined with low-dose streptozotocin (STZ), received either vehicle, low-dose A-MG (100 mg/kg/d), or high-dose A-MG (200 mg/kg/d) for 6 weeks. Cardiac function was assessed by echocardiography. H&E and Masson’s staining were used to evaluate cardiac tissue structure and fibrosis, and Western blotting was used to evaluate myocardial protein expression. Results In HG/F-induced H9C2 cells, A-MG (1 and 3 μM) significantly increased cell viability ...