Quercetin inhibits the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve sepsis-induced cardiomyopathy

Hao Zhao; Xin Lin; Qingfeng Chen; Xiaoyue Wang; Yongya Wu; Xiaoxia Zhao

doi:10.1016/j.taap.2023.116672

Quercetin inhibits the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve sepsis-induced cardiomyopathy

Toxicol Appl Pharmacol. 2023 Oct 15:477:116672. doi: 10.1016/j.taap.2023.116672. Epub 2023 Aug 28.

Authors

Hao Zhao¹, Xin Lin¹, Qingfeng Chen¹, Xiaoyue Wang¹, Yongya Wu¹, Xiaoxia Zhao²

Affiliations

¹ Department of Emergency and Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 42, Wenhuaxi Road, Lixia District, Jinan City, Shandong Province 250014, China.
² Department of Emergency and Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 42, Wenhuaxi Road, Lixia District, Jinan City, Shandong Province 250014, China. Electronic address: 71000798@sdutcm.edu.cn.

PMID: 37648089
DOI: 10.1016/j.taap.2023.116672

Abstract

Sepsis-induced cardiomyopathy (SIC) has high morbidity and mortality. Quercetin (QUE) has been used to treat many inflammatory diseases related to pyroptosis. However, its effect on SIC has not been reported before. We aimed to explore the therapeutic mechanism of QUE on SIC. We found that the expression levels of NOX2, markers of myocardial injury and inflammatory factors related to pyroptosis were upregulated in the serum of SIC patients. QUE improved the viability and reduced the death rate of LPS-treated H9C2 cells. It could downregulate the expression level of NOX2 and alleviate NOX2-induced mitochondrial damage to inhibit the ROS-mediated NF-κB/TXNIP pathway thus ameliorating cell pyroptosis. Overexpression of NOX2 partially attenuated the anti-pyroptotic effects of QUE on LPS-treated H9C2 cells in vitro. Besides, the results of animal experiments reported that the mitochondrial damage was reduced by QUE treatment, which subsequently inhibited the ROS-mediated NF-κB/TXNIP pathway to ameliorate cell pyroptosis to further alleviate myocardial injury in CLP-induced rats in vivo. To conclude, QUE suppressed the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve SIC.

Keywords: Mitochondria; Oxidative stress; Pyroptosis; Quercetin; Sepsis-induced cardiomyopathy.