Anti-inflammatory activity of Sorbus commixta water extract and its molecular inhibitory mechanism

J Ethnopharmacol. 2011 Mar 24;134(2):493-500. doi: 10.1016/j.jep.2010.12.032. Epub 2010 Dec 31.

Abstract

Ethnopharmacological significance: 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.

Aim of study: 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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Arachidonic Acid
  • Asia, Eastern
  • Dose-Response Relationship, Drug
  • Edema / drug therapy
  • HEK293 Cells
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation Mediators / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Medicine, Traditional
  • Mice
  • Mice, Inbred ICR
  • Myeloid Differentiation Factor 88 / metabolism
  • Phosphorylation
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Sorbus* / chemistry
  • Syk Kinase
  • Toll-Like Receptor 4 / metabolism
  • src-Family Kinases / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Myeloid Differentiation Factor 88
  • Plant Extracts
  • RNA, Messenger
  • Toll-Like Receptor 4
  • Arachidonic Acid
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse
  • src-Family Kinases