AUTHOR=Long Kunlan , Zhao Ziyi , Chen Jun , Zhi Lijia , Wang Chunxia , Liao Dan , Wang Meng , Gao Peiyang 

TITLE=Yang-xin-xue keli exerts therapeutic effects via regulating mitochondrial homeostasis and function in doxorubicin-induced rat heart failure

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.931453

DOI=10.3389/fphar.2022.931453

ISSN=1663-9812

ABSTRACT=Background: Heart failure, especially chronic heart failure, is generally and mainly induced by the accumulation of reactive oxygen species (ROS), as well as the subsequent loss of mitochondrial permeability transition pore (mPTP) opening and pathological mitochondrial dysfunction. Herein, we explored the therapeutic effects of the Chinese medicine Yangxin Keli (YXXKL) on chronic heart failure and its relative underlying working mechanism.
Methods: To mimic oxidative stress-induced chronic heart failure, a rat heart failure model was induced by the administration of DOX. Transthoracic echocardiography was performed to confirm the successful establishment of heart failure model by observation of significantly decreased cardiac function of rats. Mitochondrial membrane potential, function and ATP synthesis activity were measured after YXXKL was employed.
Results The administration of YXXKL not only significantly improved cardiac function but also reversed the myocardium loss and fibrosis induced via DOX. Moreover, the administration of YXXKL also increased ATP synthesis and mitochondrial DNA mass in left ventricular tissues, which indicated that mitochondria may be a key target of YXXKL. Thus, we employed rat cardiomyocyte H9c2 and primary rat cardiac myocytes (RCMs) to induce oxidative-stress-induced myocardial injury via DOX treatment. YXXKL-medicated serum promoted cell proliferation, which was inhibited by the addition of IC30 DOX, and this serum also inhibited cell apoptosis, which was promoted by the addition of IC50 DOX. YXKL-medicated serum was able to scavenge ROS and also maintained the mitochondrial membrane potential and promoted mitochondrial function, including the promotion of ATP synthesis, mitochondrial DNA mass and transcriptional activity. Furthermore, we also observed that YXXKL-medicated serum inhibited DOX-induced autophagy/mitophagy via scavenging ROS.
Conclusion Taken together, we conclude that YXXKLI may exert therapeutic effects on oxidative-stress related heart failure via the regulation of mitochondria.