Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis  

作　　者：Xingyan Zhang Xiaoyan Lian Huling Li Wenjing Zhao Xin Li Fujun Zhou Yutong Zhou Tao Cui Yuli Wang Changxiao Liu 

机构地区：[1]Key Laboratory of Quality-marker of Traditional Chinese Medicines,Tianjin Institute of Pharmaceutical Research Co.,Ltd.,Tianjin 300462,China [2]Center for Drug Evaluation,National Medical Products Administration,Beijing 100022,China [3]Department of Pharmacology,Tianjin Medical University,Tianjin 300070,China [4]State Key Laboratory of Drug Delivery Technology and Pharmacokinetics,Tianjin Institute of Pharmaceutical Research Co.,Ltd.,Tianjin 300462,China [5]Key Laboratory of Systems Bioengineering(Ministry of Education),School of Chemistry Engineering and Technology,Tianjin University,Tianjin 300072,China [6]Research Unit for Drug Metabolism,Chinese Academy of Medical Sciences,Beijing 100730,China [7]Pharmaceuticai Armaceuticai DA REN TANG Group Corporation Limited Traditional Chinese Pharmacy Researchinstitute,Tianjin 300457,China [8]Tianjin Key Laboratory of Quality Control in Chinese Medicine,Tianjin 300457,China

出　　处：《Chinese Herbal Medicines》2022年第4期554-562,F0002,共10页中草药（英文版）

基　　金：supported by Open and Selective Project of National Major New Drug Development Science and Technology Major Project in Tianjin,China(No.2017ZX09031062);National Major New Drug Innovation Project of China(No.2017ZX09101001);National Key Research and Development Project in Tianjin,China(No.2019YFA09005600);Open Research fund of State Key Laboratory of Drug Delivery Technology and Pharmacokinetics in Tianjin;China(No.010161003);CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-020);Tianjin Key Training Project for‘Project+Team’(No.XC202030)。

摘　　要：Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity.This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction.Methods:Levels of interleukin(IL)-6,IL-1βand intracellular reactive oxygen species(ROS)were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide(LPS).Subsequently,the m RNA and protein levels of inducible nitric oxide synthase(i NOS),vascular endothelial growth factor(VEGF),cyclooxygenase(COX)-2,tumor necrosis factor(TNF)-a and the phosphorylation expression levels of the MAPK signal pathway were also evaluated.A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway.And then MAPK inhibitors were used to reveal the expression level of i NOS,VEGF,COX-2 and TNF-a in RAW264.7 cells.Results:It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin.Then,the m RNA and protein levels of i NOS,VEGF,COX-2 and TNF-a were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well.In silico analysis,taxifolin could form a relatively stable combination with MAPK signal pathway.MAPK inhibitors showed increasing or decreasing effect in the m RNA levels of i NOS,VEGF,COX-2 and TNF-a,which suggesting that taxifolin down-regulated i NOS,VEGF,COX-2 and TNF-a expressions were not entirely through the MAPK pathway.Conclusion:This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

关 键 词：MAPK signal pathway molecular docking pro-inflammatory cytokines TAXIFOLIN 

分 类 号：R285[医药卫生—中药学]