title: Methanol extract of Osbeckia stellata suppresses lipopolysaccharide- and HCl/ethanol-induced inflammatory responses by inhibiting Src/Syk and IRAK1.
abstract: BACKGROUND
  Osbeckia stellata Buch.-Ham. ex D.Don is traditionally prescribed to treat various inflammatory diseases. However, how this plant is able to modulate inflammatory responses is unknown. This study explored the anti-inflammatory effects of 99% methanol extracts of O. stellata (Os-ME).
  
  
  METHODS
  The anti-inflammatory effect of Os-ME was evaluated by measuring the levels of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by determining gastric inflammatory lesions in mice induced by HCl/ethanol (EtOH). The molecular mechanisms of the inhibitions were elucidated by analyzing the activation of transcription factors, upstream signaling cascade, and the kinase activities of target enzymes.
  
  
  RESULTS
  Os-ME dose-dependently diminished the release of NO and PGE(2), and suppressed the expression of inducible NO synthase and cyclooxygenase-2 in LPS-treated RAW264.7 cells. Os-ME clearly inhibited the translocation of c-Rel, a subunit of nuclear factor κB (NF-κB), and c-Fos, a subunit of activator protein-1 (AP-1), and their regulatory upstream enzymes including Src, Syk, and IRAK1. Interestingly, orally administered Os-ME ameliorated acute inflammatory symptoms and suppressed the activation of Src, Syk, and IRAK1 induced by HCl/EtOH treatment in mouse stomach.
  
  
  CONCLUSIONS
  Os-ME can be considered as an orally available anti-inflammatory herbal remedy with Src/Syk/NF-κB and IRAK1/AP-1 inhibitory properties.
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: Sang
authors.initials: S
authors.lastname: Hyun Moh
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Jae
authors.initials: J
authors.lastname: Gwang Park
authors.forename: Deok
authors.initials: D
authors.lastname: Hyo Yoon
authors.forename: Tae
authors.initials: T
authors.lastname: Woong Kim
authors.forename: Seong
authors.initials: S
authors.lastname: Hwan Kim
authors.forename: Sukchan
authors.initials: S
authors.lastname: Lee
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Jae
authors.initials: J
authors.lastname: Youl Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D000431:Ethanol; D057809:HEK293 Cells; D006801:Humans; D006851:Hydrochloric Acid; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D035322:Melastomataceae; D000432:Methanol / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012997:Solvents; D009569:Nitric Oxide; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; D015232:Dinoprostone; D006851:Hydrochloric Acid; D000432:Methanol