Ginsenoside Rh1 mitigates mitochondrial dysfunction induced by myocardial ischaemia through its novel role as a sirtuin 3 activator

• DOI: 10.1111/bph.70022
• Publication Date: 2025-03-30T18:15:43Z
• Authors: Shuaishuai Gong; Hong Chen; Shuhua Fang; Mengyu Li; Jingui Hu; Yue Li; Boyang Yu; Junping Kou; Fang Li
• Keywords: SIRT3

Abstract Background and Purpose The sirtuin 3 (SIRT3) signalling pathway is an essential target for various cardiovascular diseases (CVDs), although effective interventions in myocardial ischaemia‐induced mitochondrial dysfunction remain to be elucidated. Here, we discovered a potent SIRT3 activator explored its efficacy mechanism against dysfunction. Experimental Approach Molecular docking screened activators among the 10 more common rare ginsenosides. In vivo, left coronary artery ligation induced ischaemia injury, followed by echocardiography, histopathology serum biochemical indicators, C57BL/6J mice. Expression levels of mitophagy dynamics‐associated proteins were examined western blot (WB), immunofluorescence (IF) immunohistochemistry (IHC). vitro, oxygen–glucose deprivation‐induced hypoxic injury neonatal rat ventricular myocytes, cell viability function investigated. small interference RNA (siRNA) was transfected into cardiomyocytes validate dynamics regulated ginsenoside Rh1. Key Results Rh1 exhibited strongest binding affinity as SIRT3. improved cardiac mitigated vivo. ameliorated oxidative stress, network morphology respiration hypoxia‐injured cardiomyocytes. bound simultaneously up‐regulated Foxo3a, facilitating nuclear translocation reducing acetylation Foxo3a. markedly promoted fusion, inhibited fission accelerated mitophagy. siRNA abrogated regulation on Conclusion Implications novel protects dysfunction, providing new clues prevent treat ischaemic injury‐associated CVD.