title: Methanol extract of Evodia lepta displays Syk/Src-targeted anti-inflammatory activity.
abstract: BACKGROUND
  Evodia lepta (Spreng.) Merr., in the Rutaceae family, is a medicinal plant traditionally used to treat inflammatory symptoms such as in meningitis and hepatitis. However, no study has systematically investigated its anti-inflammatory activities including its molecular mechanism.
  
  
  METHODS
  The effects of a methanol extract from the roots Evodia lepta (El-ME) were evaluated using lipopolysaccharide (LPS)-treated RAW264.7 cells producing nitric oxide (NO) and prostaglandin E2 (PGE2), and an HCl/ethanol-induced mouse gastritis model. Target molecules were identified by analyzing the activation of transcription factors and their upstream kinases.
  
  
  RESULTS
  El-ME reduced the production of NO and PGE2 from LPS-activated RAW264.7 cells in a dose-dependent manner. El-ME also ameliorated the gastritis symptoms of EtOH/HCl-treated mice. The extract suppressed production of mRNA for the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2; the nuclear translocation of nuclear factor (NF)-κB; the phosphorylation of upstream kinases that activate NF-κB; and the kinase activities of Syk and Src.
  
  
  CONCLUSIONS
  The anti-inflammatory effects of El-ME might be due to its suppression of Syk/Src and NF-κB. Considering the in vitro and in vivo efficacy of El-ME, Evodia lepta could be developed into an anti-inflammatory herbal remedy.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Yoon
authors.forename: Hye Yoon
authors.initials: HY
authors.lastname: Jeong
authors.forename: Shi Hyoung
authors.initials: SH
authors.lastname: Kim
authors.forename: Han Gyung
authors.initials: HG
authors.lastname: Kim
authors.forename: Gyeongsug
authors.initials: G
authors.lastname: Nam
authors.forename: Jin Pyo
authors.initials: JP
authors.lastname: Kim
authors.forename: Deok Hyo
authors.initials: DH
authors.lastname: Yoon
authors.forename: Hyunsik
authors.initials: H
authors.lastname: Hwang
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kimc
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D000431:Ethanol; D032086:Evodia; D005756:Gastritis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D006851:Hydrochloric Acid; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000432:Methanol / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013270:Stomach / Q000473:pathology; D000072377:Syk Kinase
chemical_list: D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D012997:Solvents; D009569:Nitric Oxide; D000431:Ethanol; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D015232:Dinoprostone; D006851:Hydrochloric Acid; D000432:Methanol
keywords: (TNF)-α; 3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Anti-inflammatory; CMC; COX; EIA; ELISA; Evodia lepta (Spreng.) Merr.; IκB kinase; IκBκ; Iκκ; LPS; MTT; NF-κB; NO; PG; PI3K; RT-PCR; Rutaceae; Src; Syk; TLR; Toll-like receptors (TLR); cyclooxygenase; enzyme immunoassay; enzyme-linked immunosorbent assay; iNOS; inducible NO synthase; inhibitor of kappa B alpha; lipopolysaccharide; nitric oxide; nuclear factor-κB; phosphoinositide 3-kinase; prostaglandin; reverse transcriptase-polymerase chain reaction; sodium carboxymethylcellulose; spleen tyrosine kinase; tumor necrosis factor