PMID- 31378007 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20200622 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 63 IP - 20 DP - 2019 Oct TI - A Novel Quinolyl-Substituted Analogue of Resveratrol Inhibits LPS-Induced Inflammatory Responses in Microglial Cells by Blocking the NF-kappaB/MAPK Signaling Pathways. PG - e1801380 LID - 10.1002/mnfr.201801380 [doi] AB - SCOPE: The anti-neuroinflammatory effect of a novel quinolyl-substituted analogue of resveratrol (RV01) on lipopolysaccharide (LPS)-induced microglial activation is investigated, as well as the possible underlying mechanisms. METHODS AND RESULTS: Cell viability is measured using an MTT assay. Nitric oxide (NO) release is determined by nitrite assay. The interaction between RV01 and inducible nitric oxide synthase (iNOS) is studied using molecular docking. Free radical scavenging activity and reactive oxygen species (ROS) production are determined by DPPH reduction assay and DCFH-DA assay. Pretreatment with RV01 (1-30 microm) prior to LPS (1 microg mL(-1) ) stimulation decreased NO release and iNOS expression without observable cytotoxicity. RV01 reduced the mRNA levels and secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). RV01 also inhibited LPS-induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Furthermore, RV01 decreases the protein expression of toll-like receptor 4 (TLR4) and inhibits the LPS-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear transcription factor-kappaB (NF-kappaB) signaling pathways. Additionally, conditioned medium from microglia co-treated with LPS and RV01 alleviates the death of SH-SY5Y cells induced by conditioned medium from activated N9 microglial cells. Lastly, a mouse neuroinflammation model is further used to confirm the effect of RV01 in vivo. CONCLUSION: These results show that RV01 suppresses microglia-mediated neuroinflammation and protects neurons from inflammatory damage, which indicates that RV01 has great potential as a nutritional preventive strategy for neuroinflammation-related diseases. CI - (c) 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Hou, Yue AU - Hou Y AUID- ORCID: 0000-0002-9808-0488 AD - College of Life and Health Sciences, Northeastern University, Shenyang, 110169, P. R. China. AD - Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110169, P. R. China. FAU - Zhang, Yuchen AU - Zhang Y AD - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. FAU - Mi, Yan AU - Mi Y AD - College of Life and Health Sciences, Northeastern University, Shenyang, 110169, P. R. China. AD - Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110169, P. R. China. FAU - Wang, Jian AU - Wang J AD - Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. FAU - Zhang, Haotian AU - Zhang H AD - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. FAU - Xu, Jikai AU - Xu J AD - College of Life and Health Sciences, Northeastern University, Shenyang, 110169, P. R. China. AD - Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110169, P. R. China. FAU - Yang, Yanqiu AU - Yang Y AD - College of Life and Health Sciences, Northeastern University, Shenyang, 110169, P. R. China. FAU - Liu, Jingyu AU - Liu J AD - College of Life and Health Sciences, Northeastern University, Shenyang, 110169, P. R. China. FAU - Ding, Lingling AU - Ding L AD - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. FAU - Yang, Jingyu AU - Yang J AD - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. FAU - Chen, Guoliang AU - Chen G AD - Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. FAU - Wu, Chunfu AU - Wu C AD - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190816 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.6.3.- (NADPH Oxidases) RN - Q369O8926L (Resveratrol) SB - IM MH - Animals MH - Cells, Cultured MH - Humans MH - Inflammation/*prevention & control MH - Lipopolysaccharides/pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Mice MH - Microglia/*drug effects MH - NADPH Oxidases/metabolism MH - NF-kappa B/*antagonists & inhibitors/physiology MH - Nitric Oxide/biosynthesis MH - Reactive Oxygen Species/metabolism MH - Resveratrol/*analogs & derivatives/pharmacology MH - Signal Transduction/drug effects MH - Toll-Like Receptor 4/genetics MH - Tumor Necrosis Factor-alpha/biosynthesis/genetics OTO - NOTNLM OT - (E)-5-(2-(Quinolin-4-yl)vinyl) benzene-1 OT - 3-diol (RV01), MAPKs, microglia, neuroinflammation, NF-kappaB EDAT- 2019/08/05 06:00 MHDA- 2020/06/23 06:00 CRDT- 2019/08/05 06:00 PHST- 2018/12/17 00:00 [received] PHST- 2019/07/13 00:00 [revised] PHST- 2019/08/05 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] PHST- 2019/08/05 06:00 [entrez] AID - 10.1002/mnfr.201801380 [doi] PST - ppublish SO - Mol Nutr Food Res. 2019 Oct;63(20):e1801380. doi: 10.1002/mnfr.201801380. Epub 2019 Aug 16.