Corosolic acid attenuates cardiac ischemia/reperfusion injury through the PHB2/PINK1/parkin/mitophagy pathway
Jun Zhang,
Yongjian Zhao,
Lin Yan,
Mingyue Tan,
Yifeng Jin,
Yunfei Yin,
Lianhua Han,
Xiao Ma,
Yimin Li,
Tianke Yang,
Tingbo Jiang,
Hongxia Li
Affiliations
Jun Zhang
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Yongjian Zhao
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Lin Yan
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Mingyue Tan
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Yifeng Jin
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Yunfei Yin
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Lianhua Han
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Xiao Ma
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Yimin Li
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China
Tianke Yang
Department of Ophthalmology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, P.R. China; Corresponding author
Tingbo Jiang
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China; Corresponding author
Hongxia Li
Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China; Corresponding author
Summary: Despite advances in treatment, myocardial infarction remains the leading cause of heart failure and death worldwide, and the restoration of coronary blood flow can also cause heart damage. In this study, we found that corosolic acid (CA), also known as plant insulin, significantly protects the heart from ischemia-reperfusion (I/R) injury. In addition, CA can inhibit oxidative stress and improve mitochondrial structure and function in cardiomyocytes. Subsequently, our study demonstrated that CA improved the expression of the mitophagy-related proteins Prohibitin 2 (PHB2), PTEN-induced putative kinase protein-1 (PINK1), and Parkin. Meanwhile, through molecular docking, we found an excellent binding between CA and PHB2 protein. Finally, the knockdown of PHB2 eliminated the protective effect of CA on hypoxia-reoxygenation in cardiomyocytes. Taken together, our study reveals that CA increases mitophagy in cardiomyocytes via the PHB2/PINK1/Parkin signaling pathway, inhibits oxidative stress response, and maintains mitochondrial function, thereby improving cardiac function after I/R.
