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

  • Molecules. 2018 Jun 14;23(6):1447. doi: 10.3390/molecules23061447.
Wenzhe Yu  1  2 ,  Mengru Tao  3  4 ,  Yueliang Zhao  5  6 ,  Xiaoqian Hu  7  8 ,  Mingfu Wang  9  10  11
Affiliations
  • 1. College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. [email protected].
  • 2. Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. [email protected].
  • 3. College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. [email protected].
  • 4. Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. [email protected].
  • 5. College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. [email protected].
  • 6. Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. [email protected].
  • 7. College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. [email protected].
  • 8. Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. [email protected].
  • 9. College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. [email protected].
  • 10. Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. [email protected].
  • 11. School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China. [email protected].
PMID: 29903983 DOI: 10.3390/molecules23061447
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.

Keywords
4′-methoxyresveratrol; MAPK; NF-κB; NLRP3 inflammasome; RAGE; oxidative stress.
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