title: Methanol extract of Hopea odorata suppresses inflammatory responses via the direct inhibition of multiple kinases.
abstract: BACKGROUND
  Hopea odorata Roxb. (Dipterocarpaceae) is a representative Thai ethnopharmacological herbal plant used in the treatment of various inflammation-related diseases. In spite of its traditional use, systematic studies of its anti-inflammatory action have not been performed.
  
  
  METHODS
  The inhibitory activities of a Hopea odorata methanol extract (Ho-ME) on the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin E(2) (PGE(2)) in RAW264.7 cells and peritoneal macrophages were investigated. The effects of Ho-ME on the gastritis symptoms induced by HCl/EtOH and on ear oedemas induced by arachidonic acid were also examined. Furthermore, to identify the immunopharmacological targets of this extract, nuclear fractionation, a reporter gene assay, immunoprecipitation, immunoblot analysis, and a kinase assay were employed.
  
  
  RESULTS
  Ho-ME strongly inhibited the release of NO, PGE(2), and TNF-α in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ho-ME also clearly suppressed the gene expression of pro-inflammatory cytokines and chemokines, such as interferon (IFN)-β, interleukin (IL)-12, and monocyte chemotactic protein-1 (MCP-1). By analysing the inhibited target molecules, Syk and Src were found to be suppressed in the inhibition of nuclear factor (NF)-κB pathway. In addition, the observed downregulation of activator protein (AP)-1 and cAMP response element-binding (CREB) was due to the direct inhibition of interleukin-1 receptor-associated kinase (IRAK)1 and IRAK4, which was also linked to the suppression of c-Jun N-terminal kinase (JNK) and p38. In agreement with the in vitro observations, this extract also ameliorated the inflammatory symptoms in EtOH/HCl-induced gastritis and arachidonic acid-induced ear oedemas in mice.
  
  
  CONCLUSIONS
  Ho-ME has potential as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future pre-clinical studies will be needed to investigate this possibility.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Lee
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.forename: Jueun
authors.initials: J
authors.lastname: Oh
authors.forename: Deok
authors.initials: D
authors.lastname: Jeong
authors.forename: Sukchan
authors.initials: S
authors.lastname: Lee
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
authors.forename: Yung Chul
authors.initials: YC
authors.lastname: Park
authors.forename: Gi-Ho
authors.initials: GH
authors.lastname: Sung
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D053958:Dipterocarpaceae; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal; D008297:Male; D000432:Methanol / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012997:Solvents; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D011494:Protein Kinases; D015232:Dinoprostone; D000432:Methanol