1. Academic Validation
  2. Salvianolic Acid B Alleviates Myocardial Ischemia Injury by Suppressing NLRP3 Inflammasome Activation via SIRT1-AMPK-PGC-1α Signaling Pathway

Salvianolic Acid B Alleviates Myocardial Ischemia Injury by Suppressing NLRP3 Inflammasome Activation via SIRT1-AMPK-PGC-1α Signaling Pathway

  • Cardiovasc Toxicol. 2022 Sep;22(9):842-857. doi: 10.1007/s12012-022-09760-8.
Qingju Li  # 1 2 Zhi Zuo  # 3 Yunzheng Pan 1 Qi Zhang 1 Li Xu 4 Baoping Jiang 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China.
  • 2 Department of Central Laboratory, Lianshui County People's Hospital, Kangda College of Nanjing Medical University, Huaian, 223400, China.
  • 3 Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital), Nanjing, 210029, China.
  • 4 School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China. xuli@njucm.edu.cn.
  • 5 School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China. Jiangbaoping@njucm.edu.cn.
  • # Contributed equally.
Abstract

Salvianolic acid B (SalB) has been extensively investigated in our laboratory for myocardial ischemia (MI) disease. This study mainly aimed to illustrate the relationship between SIRT1 and the therapeutic effect of SalB on MI in rats and hypoxia damage in H9c2 cells. Furthermore, whether the antagonism of NLRP3 by SalB in the injuries mentioned above is related to SIRT1-AMPK-PGC-1α pathway-mediated mitochondrial biogenesis was further investigated. In vivo, 24 h after MI surgery, we found that SalB effectively reduced ST-segment elevation, myocardial infarct size enlargement, cardiac injury markers, myocardial structural abnormalities, and myocardial apoptotic cells in MI injury rats. In vitro, after 4 h of hypoxia exposure, SalB alleviated cell injury, inhibited the production of ROS and IL-1β, and prevented the loss of mitochondrial membrane potential (MMP). Besides, SalB downregulated the critical components of the NLRP3 inflammasome and upregulated the SIRT1-AMPK-PGC-1α signaling pathway-related molecules in myocardial tissues and H9c2 cells. However, all the above protective effects of SalB on MI could be offset by EX527. Taken together, our findings indicated that SalB could attenuate MI injury by targeting NLRP3, which is at least partially dependent on the SIRT1/AMPK/PGC-1α signaling pathway.

Keywords

Myocardial ischemia; NLRP3; SIRT1-AMPK-PGC-1α; Salvianolic acid B.

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