title: Magnolol inhibits lipopolysaccharide-induced inflammatory response by interfering with TLR4 mediated NF-κB and MAPKs signaling pathways.
abstract: BACKGROUND
  Magnolia officinalis as a traditional Chinese herb has long been used for the treatment of anxiety, cough, headache and allergic diseases, and also have been used in traditional Chinese medicine to treat a variety of mental disorders including depression.
  
  
  OBJECTIVE
  Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been reported to have anti-inflammatory properties. However, the underlying molecular mechanisms are not well understood. The aim of this study was to investigate the molecular mechanism of magnolol in modifying lipopolysaccharide (LPS)-induced signal pathways in RAW264.7 cells.
  
  
  METHODS
  The purity of magnolol was determined by high performance liquid chromatography. RAW264.7 cells were stimulated with LPS in the presence or absence of magnolol. The expression of proinflammatory cytokines were determined by ELISA and reverse transcription-PCR. Nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and Toll-like receptor 4 (TLR4) were determined by Western blot. Further analyses were performed on mTLR4 and mMD2 co-transfected HEK293 cells.
  
  
  RESULTS
  The result showed that the purity of magnolol used in this study was 100%. Magnolol inhibited the expression of TNF-α, IL-6 and IL-1β in LPS-stimulated RAW264.7 cells in a dose-dependent manner. Western blot analysis showed that magnolol suppressed LPS-induced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK and P38. Magnolol could significantly down-regulated the expression of TLR4 stimulating by LPS. Furthermore, magnolol suppressed LPS-induced IL-8 production in HEK293-mTLR4/MD-2 cells.
  
  
  CONCLUSIONS
  Our results suggest that magnolol exerts an anti-inflammatory property by down-regulated the expression of TLR4 up-regulated by LPS, thereby attenuating TLR4 mediated the activation of NF-κB and MAPK signaling and the release of pro-inflammatory cytokines. These findings suggest that magnolol may be a therapeutic agent against inflammatory diseases.
authors.affiliation: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China. fuyunhesky@sina.com
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Fu
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Naisheng
authors.initials: N
authors.lastname: Zhang
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Dejie
authors.initials: D
authors.lastname: Liang
authors.forename: Fengyang
authors.initials: F
authors.lastname: Li
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Cao
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Feng
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D016209:Interleukin-8 / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D014162:Transfection / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D016207:Cytokines; D016209:Interleukin-8; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; C005498:magnolol