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Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress

Resveratrol shows promizing anti-inflammatory effects in recent clinical trials, however its function in cardiovascular patients remains conflicting, suggesting there may be new mechanisms underlying its cardioprotective activity. Acute sympathetic stress induces early activation of the NLR family,...

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Autores principales: Wang, Rui, Wang, Yanming, Wu, Jimin, Guo, Yanli, Xiao, Han, Zhang, Youyi, Ma, Ketao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891986/
https://www.ncbi.nlm.nih.gov/pubmed/35250567
http://dx.doi.org/10.3389/fphar.2022.818127
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author Wang, Rui
Wang, Yanming
Wu, Jimin
Guo, Yanli
Xiao, Han
Zhang, Youyi
Ma, Ketao
author_facet Wang, Rui
Wang, Yanming
Wu, Jimin
Guo, Yanli
Xiao, Han
Zhang, Youyi
Ma, Ketao
author_sort Wang, Rui
collection PubMed
description Resveratrol shows promizing anti-inflammatory effects in recent clinical trials, however its function in cardiovascular patients remains conflicting, suggesting there may be new mechanisms underlying its cardioprotective activity. Acute sympathetic stress induces early activation of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome in cardiomyocytes as a critical step for triggering cardiac inflammation. Thus, this study explored targets of resveratrol activity involved in the inhibition of early inflammasome activation in cardiomyocytes following acute sympathetic stress. Network pharmacology was used to analyze common candidate targets in the sympathetic stress pathway, resveratrol activity, and myocardial inflammation and showed the Phosphoinositol 3—kinase (PI3K)/serine threonine protein kinase (Akt) signaling pathway and the target AKT1 may play a critical role. Molecular docking provided support for potential binding of resveratrol on AKT1. Furthermore, the effect of resveratrol on AKT1 activation was determined in cardiomyocytes. resveratrol dose-dependently inhibited AKT1 activation after activation of β-adrenoceptor. The AKT1 inhibitor A-674563 suppressed the activation of the NLRP3 inflammasome in cardiomyocytes following β-adrenoceptor activation, suggesting that AKT1 is a critical regulator molecule upstream of the NLRP3 inflammasome. Consistently, treatment with resveratrol suppressed β-adrenoceptor-mediated NLRP3 inflammasome activation in both cardiomyocytes and mouse hearts, as well as the resultant cardiac inflammation. In conclusion, resveratrol targets AKT1 to inhibit NLRP3 inflammasome activation in cardiomyocytes and cardiac inflammation following acute sympathetic stress. AKT1 is an important target of resveratrol, which should be considered as a treatment option for cardiovascular patients, especially those at risk of acute sympathetic stress.
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spelling pubmed-88919862022-03-04 Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress Wang, Rui Wang, Yanming Wu, Jimin Guo, Yanli Xiao, Han Zhang, Youyi Ma, Ketao Front Pharmacol Pharmacology Resveratrol shows promizing anti-inflammatory effects in recent clinical trials, however its function in cardiovascular patients remains conflicting, suggesting there may be new mechanisms underlying its cardioprotective activity. Acute sympathetic stress induces early activation of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome in cardiomyocytes as a critical step for triggering cardiac inflammation. Thus, this study explored targets of resveratrol activity involved in the inhibition of early inflammasome activation in cardiomyocytes following acute sympathetic stress. Network pharmacology was used to analyze common candidate targets in the sympathetic stress pathway, resveratrol activity, and myocardial inflammation and showed the Phosphoinositol 3—kinase (PI3K)/serine threonine protein kinase (Akt) signaling pathway and the target AKT1 may play a critical role. Molecular docking provided support for potential binding of resveratrol on AKT1. Furthermore, the effect of resveratrol on AKT1 activation was determined in cardiomyocytes. resveratrol dose-dependently inhibited AKT1 activation after activation of β-adrenoceptor. The AKT1 inhibitor A-674563 suppressed the activation of the NLRP3 inflammasome in cardiomyocytes following β-adrenoceptor activation, suggesting that AKT1 is a critical regulator molecule upstream of the NLRP3 inflammasome. Consistently, treatment with resveratrol suppressed β-adrenoceptor-mediated NLRP3 inflammasome activation in both cardiomyocytes and mouse hearts, as well as the resultant cardiac inflammation. In conclusion, resveratrol targets AKT1 to inhibit NLRP3 inflammasome activation in cardiomyocytes and cardiac inflammation following acute sympathetic stress. AKT1 is an important target of resveratrol, which should be considered as a treatment option for cardiovascular patients, especially those at risk of acute sympathetic stress. Frontiers Media S.A. 2022-02-17 /pmc/articles/PMC8891986/ /pubmed/35250567 http://dx.doi.org/10.3389/fphar.2022.818127 Text en Copyright © 2022 Wang, Wang, Wu, Guo, Xiao, Zhang and Ma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Rui
Wang, Yanming
Wu, Jimin
Guo, Yanli
Xiao, Han
Zhang, Youyi
Ma, Ketao
Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress
title Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress
title_full Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress
title_fullStr Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress
title_full_unstemmed Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress
title_short Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress
title_sort resveratrol targets akt1 to inhibit inflammasome activation in cardiomyocytes under acute sympathetic stress
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891986/
https://www.ncbi.nlm.nih.gov/pubmed/35250567
http://dx.doi.org/10.3389/fphar.2022.818127
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