title: Concurrent suppression of NF-κB, p38 MAPK and reactive oxygen species formation underlies the effect of a novel compound isolated from Curcuma comosa Roxb. in LPS-activated microglia.
abstract: OBJECTIVE
  We investigated the molecular mechanisms underlying the effect of (3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol, also known as compound 092, isolated from Curcuma comosa Roxb on the production of pro-inflammatory mediators and oxidative stress in lipopolysaccharide (LPS)-activated highly aggressive proliferating immortalized (HAPI) microglial cell lines.
  
  
  METHODS
  Nitric oxide (NO) production was determined using the Griess reaction, and reverse transcription polymerase chain reaction was used to measure the expression of inducible nitric oxide synthase (iNOS) mRNA. Western blotting was used to determine the levels of pro-inflammatory mediators and their related upstream proteins.
  
  
  RESULTS
  Compound 092 suppressed NO production and iNOS expression in LPS-stimulated HAPI cells. These effects originated from the ability of compound 092 to attenuate the activation of nuclear factor (NF)-κB as determined by the reduction in p-NF-κB and p-IκB kinase (IKK) protein levels. Compound 092 also significantly lowered LPS-activated intracellular reactive oxygen species production and p38 mitogen-activated protein kinase (MAPK) activation.
  
  
  CONCLUSIONS
  Compound 092 suppresses microglial activation through attenuation of p38 MAPK and NF-κB activation. Compound 092 thus holds the potential to treat neurodegenerative disorders associated with neuroinflammation and oxidative stress.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Jiamvoraphong
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Nattinee
authors.initials: N
authors.lastname: Jantaratnotai
authors.affiliation: Department of Surgery and Oral Medicine, Faculty of Dentistry, Srinakharinwirot University, Bangkok, Thailand.
authors.forename: Pantip
authors.initials: P
authors.lastname: Sanvarinda
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Pawinee
authors.initials: P
authors.lastname: Piyachaturawat
authors.affiliation: Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand.
authors.forename: Anusorn
authors.initials: A
authors.lastname: Thampithak
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Pimtip
authors.identifier: http://orcid.org/0000-0003-2430-1580
authors.initials: P
authors.lastname: Sanvarinda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D030024:Curcuma / Q000737:chemistry*; D036381:Diarylheptanoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C000626516:(3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol; D036381:Diarylheptanoids; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 
  Curcuma comosa
  ; NF-κB; inflammation; microglia; p38 MAPK; reactive oxygen species