Cyclovirobuxine D ameliorates cardiomyocyte senescence in diabetic cardiomyopathy mice by enhancing mitochondrial function via sirtuin 3–ATP5O signal axis

作者：Jiangfei An, Hang Su, Xueting Wang, Guangqiong Zhang, Chao-da Xiao, BarBu Wollenberga, Yongxin Chen, Hong Yang, Hong Luo, Long Yang, Lingyun Fu, Yini Xu, Ling Tao, Xiangchun Shen · 发表于：Chinese Medicine · 年份：2025 · DOI：10.1186/s13020-025-01254-3 · 被引用次数：2 · 研究领域：Sirtuins and Resveratrol in Medicine、Cardiovascular Function and Risk Factors、Cardiac Ischemia and Reperfusion

BACKGROUND: Diabetic cardiomyopathy (DCM) is a cardiovascular complication, with cardiomyocyte senescence being a key pathological process. Cyclovirobuxine D (CVB-D), the active compound in Buxus sinica (Rehd. et Wils.) var. parvifolia M. Cheng. CVB-D has potentially promising diabetes-related cardiomyocyte senescence-mitigating effects. Nevertheless, the impact of CVB-D on inhibiting cardiomyocyte senescence has not been widely investigated and molecular mechanisms remain ambiguous. METHODS: A diabetic mouse model was established via a high-fat diet (HFD) combined with streptozotocin (STZ). Sirtuin 3 (SIRT3) knockout, SIRT3 overexpression, and ATP5O knockout mouse models were constructed through 4-week intravenous injections of AAV9-U6-SIRT3, AAV9-CMV-SIRT3, AAV9-U6-ATP5O, and their negative controls (AAV9-CMV-NC and AAV9-U6-NC). A primary mice cardiomyocytes (NMVMs) senescence model was developed using high palmitic acid and high glucose (PA/HG). Western blotting, reverse transcription-quantitative PCR (qRT-PCR), immunofluorescence, β-galactosidase staining and flow cytometry were performed to determine the protective role of CVB-D against cardiomyocyte senescence. The underlying mechanisms of CVB-D were investigated via molecular docking, coimmunoprecipitation (Co-IP), microscale thermophoresis (MST), surface plasmon resonance (SPR) binding assay, isothermal titration calorimetry (ITC) and LC-MS/MS analysis. RESULTS: CVB-D treatment improves mitochondrial dysfunction in DC...