PMID- 29903983 OWN - NLM STAT- MEDLINE DCOM- 20181029 LR - 20230928 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 23 IP - 6 DP - 2018 Jun 14 TI - 4'-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-kappaB and NLRP3 Inflammasome Pathway. LID - 10.3390/molecules23061447 [doi] LID - 1447 AB - 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 1beta (IL-1beta), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) 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-kappaB 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-1beta. Taken together, our results suggest that the anti-inflammatory effect of 4'MR is mainly through suppressing RAGE-mediated MAPK/NF-kappaB signaling pathway and NLRP3 inflammasome activation. 4'MR could be a novel therapeutic agent for inflammation-related diseases. FAU - Yu, Wenzhe AU - Yu W AD - College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. wzyu0129@outlook.com. AD - Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. wzyu0129@outlook.com. FAU - Tao, Mengru AU - Tao M AD - College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. tmemory139@163.com. AD - Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. tmemory139@163.com. FAU - Zhao, Yueliang AU - Zhao Y AD - College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. ylzhao@shou.edu.cn. AD - Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. ylzhao@shou.edu.cn. FAU - Hu, Xiaoqian AU - Hu X AD - College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. xqhu@shou.edu.cn. AD - Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. xqhu@shou.edu.cn. FAU - Wang, Mingfu AU - Wang M AD - College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu Cheng Huan Road, LinGang New City, Shanghai 201306, China. mfwang@shou.edu.cn. AD - Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China. mfwang@shou.edu.cn. AD - School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China. mfwang@shou.edu.cn. LA - eng PT - Journal Article DEP - 20180614 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (4'-methoxyresveratrol) RN - 0 (Ager protein, mouse) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cytokines) RN - 0 (Glycation End Products, Advanced) RN - 0 (NF-kappa B) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Plant Extracts) RN - 0 (Polyphenols) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Stilbenes) RN - Q369O8926L (Resveratrol) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/chemistry/*pharmacology MH - Cytokines/metabolism MH - Dipterocarpaceae/chemistry MH - Gene Expression Regulation/drug effects MH - Glycation End Products, Advanced/*adverse effects MH - Mice MH - NF-kappa B/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Oxidative Stress/drug effects MH - Plant Extracts/chemistry/pharmacology MH - Polyphenols/chemistry/*pharmacology MH - RAW 264.7 Cells MH - Receptor for Advanced Glycation End Products/*metabolism MH - Resveratrol MH - Signal Transduction/*drug effects MH - Stilbenes/*chemistry PMC - PMC6100160 OTO - NOTNLM OT - 4'-methoxyresveratrol OT - MAPK OT - NF-kappaB OT - NLRP3 inflammasome OT - RAGE OT - oxidative stress COIS- The authors declare no conflict of interest. EDAT- 2018/06/16 06:00 MHDA- 2018/10/30 06:00 PMCR- 2018/06/14 CRDT- 2018/06/16 06:00 PHST- 2018/05/28 00:00 [received] PHST- 2018/06/13 00:00 [revised] PHST- 2018/06/13 00:00 [accepted] PHST- 2018/06/16 06:00 [entrez] PHST- 2018/06/16 06:00 [pubmed] PHST- 2018/10/30 06:00 [medline] PHST- 2018/06/14 00:00 [pmc-release] AID - molecules23061447 [pii] AID - molecules-23-01447 [pii] AID - 10.3390/molecules23061447 [doi] PST - epublish SO - Molecules. 2018 Jun 14;23(6):1447. doi: 10.3390/molecules23061447.