title: Anti-inflammatory activity of Sorbus commixta water extract and its molecular inhibitory mechanism.
abstract: BACKGROUND
  Sorbus commixta Hedl. (Rosaceae) is a well known traditionally valuable medicinal plant in Korea, China and Japan. This plant has been prescribed for long time for various inflammatory symptoms such as asthma, bronchitis, gastritis and dropsy.
  
  
  OBJECTIVE
  Although a number of pharmacological properties have already been demonstrated, the anti-inflammatory effect of this plant and its associated molecular mechanisms has not yet been fully investigated.
  
  
  METHODS
  In order to address the anti-inflammatory activity of S. commixta water extract (Sc-WE), lipopolysaccharide (LPS)-stimulated macrophages were employed and production of inflammatory mediators by these cells were evaluated.
  
  
  RESULTS
  Sc-WE significantly suppressed the production of nitric oxide (NO) and prostaglandin (PG)E(2) in a dose-dependent manner and blocked ear edema formation induced by arachidonic acid in mouse. In addition, this extract effectively diminished the mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, indicating that the inhibition occurs at the transcriptional level. Interestingly, Sc-WE remarkably blocked NF-κB translocation and its upstream signaling events by inhibition of κBα (IκBα), IκBα kinase (IKK), Akt (protein kinase B), phosphoinositide-dependent kinase 1 (PDK1), p85/phosphoinositide-3-kinase (PI3K), as per the results obtained from the reporter gene assay and immunoblotting analysis. More intriguingly, Sc-WE suppressed activities of Src and Syk kinases as well as their phosphorylation levels without altering molecular complex formation between them and toll like receptor (TLR)4 or MyD88, an adaptor protein of TLR4-mediated signaling.
  
  
  CONCLUSIONS
  Therefore, our results suggest that Sc-WE can be developed as a potent anti-inflammatory remedy, acting by suppressing the inflammatory signaling cascade composed of Src, Syk, and NF-κB.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Jang
authors.forename: Ae Ra
authors.initials: AR
authors.lastname: Kim
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Lee
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D005202:Asia, Eastern; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D008519:Medicine, Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D031994:Sorbus / Q000737:chemistry; D000072377:Syk Kinase; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D010936:Plant Extracts; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D016718:Arachidonic Acid; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases