title: Syk/Src-targeted anti-inflammatory activity of Codariocalyx motorius ethanolic extract.
abstract: BACKGROUND
  Codariocalyx motorius (Houtt.) H. Ohashi (Fabaceae) is one of several ethnopharmacologically valuable South Asian species prescribed as an herbal medicine for various inflammatory diseases. Due to the lack of systematic studies on this plant, we aimed to explore the inhibitory activity of Codariocalyx motorius toward inflammatory responses using its ethanolic extract (Cm-EE).
  
  
  METHODS
  Lipopolysaccharide (LPS)-treated macrophages and a HCl/EtOH-induced gastritis model were used for evaluation of the anti-inflammatory activity of Cm-EE. HPLC and spectroscopic analysis were employed to identify potential active components. Mechanistic approaches to determine target enzymes included kinase assays, reporter gene assays, and overexpression of target enzymes.
  
  
  RESULTS
  Cm-EE strongly suppressed nitric oxide (NO) and prostaglandin E2 (PGE2) release. Cm-EE-mediated inhibition was observed at the transcriptional level in the form of suppression of NF-κB (p65) translocation and activation. This extract also lowered the levels of phosphorylation of Src and Syk, their kinase activity, and their formation of signalling complexes by binding to the downstream enzyme p85/PI3K. In accord with these findings, the phosphorylation of p85 induced by overexpression of Src or Syk was also diminished by Cm-EE. Orally administered Cm-EE clearly inhibited gastritic ulcer formation and the phosphorylation of IκBα and Src in HCl/EtOH-treated stomachs of mice. By phytochemical analysis, luteolin and its glycoside, apigenin-7-O-glucuronide, and scutellarein-6-O-glucuronide were identified as major components of Cm-EE. Among these, it was found that luteolin was able to strongly suppress NO and PGE2 production under the same conditions.
  
  
  CONCLUSIONS
  Syk/Src-targeted inhibition of NF-κB by Cm-EE could be a major anti-inflammatory mechanism contributing to its ethno pharmacological role as an anti-inflammatory herbal medicine.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.affiliation: College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
authors.forename: Kee Dong
authors.initials: KD
authors.lastname: Yoon
authors.affiliation: Department of Forest Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Woo-Shin
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Shi Hyoung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Nak Yoon
authors.initials: NY
authors.lastname: Sung
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Baek
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Popa Mountain Park, Forest Department, Kyaukpadaung Township, Mandalay Division, Myanmar.
authors.forename: Khin Myo
authors.initials: KM
authors.lastname: Htwe
authors.affiliation: Department of Life Science, Hallym University, Chuncheon 200-702, Republic of Korea.
authors.forename: Young-Dong
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jhkim1@chonbuk.ac.kr.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jaecho@skku.edu.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000737:chemistry; D007887:Fabaceae / Q000737:chemistry*; D005756:Gastritis / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; D000431:Ethanol; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases; D015232:Dinoprostone
keywords: Anti-inflammatory effects; Apigenin-7-O-glucuronide (Pubchem CID: 5319484); Codariocalyx motorius (Houtt.) H. Ohashi (Fabaceae); Fabaceae; Luteolin; Luteolin (Pubchem CID: 5280445); Luteolin-7-O-glucuronide (Pubchem CID: 25245094); Nitric oxide; Prostaglandin E2; Scutellarein-6-O-glucuronide (Pubchem CID: 44258424)