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Molecules 2018, 23(6), 1447; https://doi.org/10.3390/molecules23061447

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

1,2
,
1,2
,
1,2
,
1,2,* and 1,2,3,*
1
College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China
2
Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China
3
School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China
*
Authors to whom correspondence should be addressed.
Received: 28 May 2018 / Revised: 13 June 2018 / Accepted: 13 June 2018 / Published: 14 June 2018
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Abstract

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. View Full-Text
Keywords: 4′-methoxyresveratrol; MAPK; oxidative stress; RAGE; NF-κB; NLRP3 inflammasome 4′-methoxyresveratrol; MAPK; oxidative stress; RAGE; NF-κB; NLRP3 inflammasome
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Yu, W.; Tao, M.; Zhao, Y.; Hu, X.; Wang, M. 4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway. Molecules 2018, 23, 1447.

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