The ability of an ethanol extract of Cinnamomum cassia to inhibit Src and spleen tyrosine kinase activity contributes to its anti-inflammatory action

J Ethnopharmacol. 2012 Jan 31;139(2):566-73. doi: 10.1016/j.jep.2011.11.051. Epub 2011 Dec 7.

Abstract

Ethnopharmacological relevance: Cinnamomum cassia Blume (Aceraceae) has been traditionally used to treat various inflammatory diseases such as gastritis. However, the anti-inflammatory mechanism of Cinnamomum cassia has not been fully elucidated. This study examined the anti-inflammatory mechanism of 95% ethanol extract (Cc-EE) of Cinnamomum cassia.

Materials and methods: The effect of Cc-EE on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages was investigated. Molecular mechanisms underlying the effects, especially inhibitory effects, was elucidated by analyzing the activation of transcription factors and their upstream signaling, and by evaluating the kinase activity of target enzymes.

Results: Cc-EE of Cinnamomum cassia diminished the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin (PG)E(2), in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. Cc-EE also blocked mRNA expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by suppressing the activation of nuclear factor (NF)-κB, and simultaneously inhibited its upstream inflammatory signaling cascades, including spleen tyrosine kinase (Syk) and Src. Consistent with these findings, the extract directly blocked the kinase activities of Src and Syk.

Conclusion: Cc-EE exerts strong anti-inflammatory activity by suppressing Src/Syk-mediated NF-κB activation, which contributes to its major ethno-pharmacological role as an anti-gastritis remedy. Future work will be focused on determining whether the extract can be further developed as an anti-inflammatory drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Cinnamomum aromaticum* / chemistry
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Ethanol / chemistry*
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / isolation & purification
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Solvents / chemistry*
  • Syk Kinase
  • Transfection
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Solvents
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Ethanol
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse
  • src-Family Kinases
  • Dinoprostone