title: Methyl-1-hydroxy-2-naphthoate, a novel naphthol derivative, inhibits lipopolysaccharide-induced inflammatory response in macrophages via suppression of NF-κB, JNK and p38 MAPK pathways.
abstract: OBJECTIVE
  The anti-inflammatory effect of methyl-1-hydroxy-2-naphthoate (MHNA), a novel naphthol derivative, was evaluated in the lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages.
  
  
  METHODS
  The release of nitric oxide (NO), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were detected by the Griess reagent and ELISA methods. The protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined by Western blotting. The mRNA expressions of IL-1β, IL-6, iNOS and COX-2 were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways were detected by Western blotting, reporter gene assay and electrophoretic mobility shift assay.
  
  
  RESULTS
  MHNA significantly inhibited the release of NO, IL-1β and IL-6 as well as the protein expression of iNOS and COX-2 in LPS-stimulated macrophages. It also inhibited the mRNA expression of iNOS, COX-2, IL-1β and IL-6. Further studies indicated that MHNA inhibited LPS-induced increases in NF-κB DNA-binding activity and NF-κB transcriptional activity as well as IκB-α degradation and NF-κB translocation in a dose-dependent manner. Meanwhile, the activation of p38 MAPK and c-Jun N-terminal kinases (JNK) induced by LPS were decreased by MHNA.
  
  
  CONCLUSIONS
  MHNA inhibits the LPS-induced inflammatory response in murine macrophages via suppression of NF-κB and MAPKs signaling pathways activation.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Guang-Fa
authors.initials: GF
authors.lastname: Wang
authors.forename: Peng-Jiu
authors.initials: PJ
authors.lastname: Yu
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Wu
authors.forename: Zheng-Guang
authors.initials: ZG
authors.lastname: Zhu
authors.forename: Zhong-Huang
authors.initials: ZH
authors.lastname: Li
authors.forename: Yuan-Xin
authors.initials: YX
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009284:Naphthols / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009284:Naphthols; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C050175:1-hydroxy-2-naphthoic acid