TY - JOUR
T1 - Ilex pubescens inhibits pyroptosis post-myocardial infarction through suppression of the ROS/NLRP3 pathway
AU - Chen, Ting fang
AU - Jue, Xiao yu
AU - Chen, Jun bang
AU - Deng, Bo
AU - Zeng, Ke feng
AU - Chen, Si
AU - Tan, Zhang bin
AU - Tan, Yong zhen
AU - Liu, Bin
AU - Zhang, Jing-zhi
AU - Zhang, Shuang-wei
N1 - Funding Information:
This work was funded by the following grants: National Natural Science Foundation of China (grant nos. 82374341, 81973830, 82374183, 82274246, 82204991), Planned Science Technology Project of Guangzhou (no. 2023A03J0419 and 2023A03J0420), General Project of Natural Science Foundation of Guangdong Province (no. 2023A1515011090), Basic and Applied Basic Research Foundation of Guangdong Province (nos. 2021A151510809), Project of Administration of Traditional Chinese Medicine of Guangdong Province of China (no. 20223013).
Publisher Copyright:
© 2024 The Author(s). Published by Elsevier B.V.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - Ilex pubescens
KW - Myocardial infarction
KW - NLRP3
KW - Pyroptosis
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=85195282893&partnerID=8YFLogxK
U2 - 10.1016/j.prmcm.2024.100455
DO - 10.1016/j.prmcm.2024.100455
M3 - Journal article
AN - SCOPUS:85195282893
SN - 2667-1425
VL - 11
JO - Pharmacological Research - Modern Chinese Medicine
JF - Pharmacological Research - Modern Chinese Medicine
M1 - 100455
ER -
