Kanglexin delays heart aging by promoting mitophagy

• 作者: Hui-min Li Xin Liu Zi-yu Meng Lei Wang Li-min Zhao Hui Chen Zhi-xia Wang Hao Cui Xue-qing Tang Xiao-han Li Wei-na Han Xue Bai Yuan Lin Heng Liu Yong Zhang Bao-feng Yang
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: Cardiovascular Pharmacology
• 页码范围: 613-623
• 页数: 11页
• 语种: 英文

摘要

Heart aging is characterized by structural and diastolic dysfunction of the heart.However,there is still no effective drug to prevent and treat the abnormal changes in cardiac function caused by aging.Here,we present the preventive effects of emodin and its derivative Kanglexin(KLX)against heart aging.We found that the diastolic dysfunction and cardiac remodeling in mice with D-galactose(D-gal)-induced aging were markedly mitigated by KLX and emodin.In addition,the senescence of neonatal mouse cardiomyocytes induced by D-gal was also reversed by KLX and emodin treatment.However,KLX exhibited better anti-heart aging effects than emodin at the same dose.Dysregulated mitophagy was observed in aging hearts and in senescent neonatal mouse cardiomyocytes,and KLX produced a greater increase in mitophagy than emodin.The mitophagy-promoting effects of KLX and emodin were ascribed to their abilities to enhance the protein stability of Parkin,a key modulator in mitophagy,with different potencies.Molecular docking and SPR analysis demonstrated that KLX has a higher affinity for the ubiquitin-like(UBL)domain of Parkin than emodin.The UBL domain might contribute to the stabilizing effects of KLX on Parkin.In conclusion,this study identifies KLX and emodin as effective anti-heart aging drugs that activate Parkin-mediated mitophagy and outlines their putative therapeutic importance.