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4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway

Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought...

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Autores principales: Yu, Wenzhe, Tao, Mengru, Zhao, Yueliang, Hu, Xiaoqian, Wang, Mingfu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100160/
https://www.ncbi.nlm.nih.gov/pubmed/29903983
http://dx.doi.org/10.3390/molecules23061447
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author Yu, Wenzhe
Tao, Mengru
Zhao, Yueliang
Hu, Xiaoqian
Wang, Mingfu
author_facet Yu, Wenzhe
Tao, Mengru
Zhao, Yueliang
Hu, Xiaoqian
Wang, Mingfu
author_sort Yu, Wenzhe
collection PubMed
description Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4′MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4′MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Besides, 4′MR significantly decreased oxidative stress, demonstrated by levels of ROS production, protein carbonyl and advanced oxidation protein product via down-regulation of NADPH oxidase. Further analysis showed that 4′MR attenuated the RAGE overexpression induced by MGO-BSA. It also blocked the downstream signal of AGE-RAGE, particularly, MAPKs including p38 and JNK, and subsequently reduced NF-κB activation. Additionally, 4′MR significantly abated the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome including NLRP3 and cleaved caspase-1 and reduced the secretion of mature IL-1β. Taken together, our results suggest that the anti-inflammatory effect of 4′MR is mainly through suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. 4′MR could be a novel therapeutic agent for inflammation-related diseases.
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spelling pubmed-61001602018-11-13 4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway Yu, Wenzhe Tao, Mengru Zhao, Yueliang Hu, Xiaoqian Wang, Mingfu Molecules Article Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4′MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4′MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Besides, 4′MR significantly decreased oxidative stress, demonstrated by levels of ROS production, protein carbonyl and advanced oxidation protein product via down-regulation of NADPH oxidase. Further analysis showed that 4′MR attenuated the RAGE overexpression induced by MGO-BSA. It also blocked the downstream signal of AGE-RAGE, particularly, MAPKs including p38 and JNK, and subsequently reduced NF-κB activation. Additionally, 4′MR significantly abated the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome including NLRP3 and cleaved caspase-1 and reduced the secretion of mature IL-1β. Taken together, our results suggest that the anti-inflammatory effect of 4′MR is mainly through suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. 4′MR could be a novel therapeutic agent for inflammation-related diseases. MDPI 2018-06-14 /pmc/articles/PMC6100160/ /pubmed/29903983 http://dx.doi.org/10.3390/molecules23061447 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Wenzhe
Tao, Mengru
Zhao, Yueliang
Hu, Xiaoqian
Wang, Mingfu
4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway
title 4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway
title_full 4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway
title_fullStr 4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway
title_full_unstemmed 4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway
title_short 4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway
title_sort 4′-methoxyresveratrol alleviated age-induced inflammation via rage-mediated nf-κb and nlrp3 inflammasome pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100160/
https://www.ncbi.nlm.nih.gov/pubmed/29903983
http://dx.doi.org/10.3390/molecules23061447
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