Ilex pubescens inhibits pyroptosis post-myocardial infarction through suppression of the ROS/NLRP3 pathway

Ting-fang Chen; Xiao-yu Jue; Jun-bang Chen; Bo Deng; Ke-feng Zeng; Si Chen; Zhang-bin Tan; Yong-zhen Tan; Bin Liu; Jing-zhi Zhang; Shuang-wei Zhang

Pharmacological Research - Modern Chinese Medicine (Jun 2024)

Ilex pubescens inhibits pyroptosis post-myocardial infarction through suppression of the ROS/NLRP3 pathway

Ting-fang Chen,
Xiao-yu Jue,
Jun-bang Chen,
Bo Deng,
Ke-feng Zeng,
Si Chen,
Zhang-bin Tan,
Yong-zhen Tan,
Bin Liu,
Jing-zhi Zhang,
Shuang-wei Zhang

Affiliations

Ting-fang Chen: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Xiao-yu Jue: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Jun-bang Chen: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Bo Deng: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Ke-feng Zeng: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Si Chen: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China; School of Chinese medicine, Hong Kong Baptist University (HKBU), Kowloon Tong, Kowloon, Hong Kong, PR China
Zhang-bin Tan: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Yong-zhen Tan: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Bin Liu: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China; Corresponding authors at: Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou 510260, PR China.
Jing-zhi Zhang: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China; Corresponding authors at: Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou 510260, PR China.
Shuang-wei Zhang: Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China; Corresponding authors at: Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou 510260, PR China.

Journal volume & issue: Vol. 11
p. 100455

Abstract

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Introduction: Ilex pubescens (IPES), a traditional Chinese herb widely used in cardiovascular diseases, has shown potential anti-inflammatory capabilities in myocardial infarction. Reactive Oxygen Species (ROS) and the NOD-like Receptor Protein 3 (NLRP3) pathway are significant contributors to aseptic inflammation in heart diseases. This study aims to elucidate the primary mechanism by which IPES inhibits pyroptosis post-myocardial infarction. Methods: By ligating the left coronary artery in C57BL/6 mice, a myocardial infarction model was established to be conducted in vivo. To establish pyroptosis in vitro, primary neonatal cardiomyocytes, extracted from the hearts of Sprague-Dawley rats, were treated in an oxygen-glucose deprivation way. ROS scavenger, NLRP3 inhibitor, and NLRP3 was overexpressed by adenovirus to confirm IPES inhibiting myocardial pyroptosis through the ROS/NLRP3 pathway. Results: In vivo, IPES exerted significant cardioprotective effects, as evidenced by reducing heart injury, improving cardiac function, and decreasing serum markers of cardiac damage. Furthermore, IPES treatment significantly inhibits ROS generation and reduces the expression levels of NLRP3 and its downstream pyroptosis-related proteins. In vitro, IPES therapy significantly decreased cell damage and pyroptosis in a concentration-dependent manner in an oxygen-glucose deprivation/re-oxygenation (OGD/R) cell model. Additionally, IPES demonstrates synergistic cardiomyocyte protection with the ROS scavenger NAC, whereas its inhibition of pyroptosis is not significantly different from that of the NLRP3 inhibitor. More importantly, the inhibitory impacts of IPES on pyroptosis were partially reversed by NLRP3 overexpression. The active components of IPES exhibit the ability to stably and efficiently bind with NLRP3. Discussion: These results demonstrate that IPES inhibit pyroptosis post-MI by suppressing the ROS/NLRP3 pathway, providing a new insight into its potential application in treating MI.

Published in Pharmacological Research - Modern Chinese Medicine

ISSN: 2667-1425 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Other systems of medicine; Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research-modern-chinese-medicine

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