1. Academic Validation
  2. A Novel Quinolyl-Substituted Analogue of Resveratrol Inhibits LPS-Induced Inflammatory Responses in Microglial Cells by Blocking the NF-κB/MAPK Signaling Pathways

A Novel Quinolyl-Substituted Analogue of Resveratrol Inhibits LPS-Induced Inflammatory Responses in Microglial Cells by Blocking the NF-κB/MAPK Signaling Pathways

  • Mol Nutr Food Res. 2019 Oct;63(20):e1801380. doi: 10.1002/mnfr.201801380.
Yue Hou 1 2 Yuchen Zhang 3 Yan Mi 1 2 Jian Wang 4 Haotian Zhang 3 Jikai Xu 1 2 Yanqiu Yang 1 Jingyu Liu 1 Lingling Ding 3 Jingyu Yang 3 Guoliang Chen 4 Chunfu Wu 3
Affiliations

Affiliations

  • 1 College of Life and Health Sciences, Northeastern University, Shenyang, 110169, P. R. China.
  • 2 Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110169, P. R. China.
  • 3 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
  • 4 Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Abstract

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 µm) prior to LPS (1 µg mL-1 ) stimulation decreased NO release and iNOS expression without observable cytotoxicity. RV01 reduced the mRNA levels and secretion of tumor necrosis factor-α (TNF-α) 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-κB (NF-κB) 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.

Keywords

(E)-5-(2-(Quinolin-4-yl)vinyl) benzene-1; 3-diol (RV01), MAPKs, microglia, neuroinflammation, NF-κB.

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