2,8-Decadiene-1,10-Diol Inhibits Lipopolysaccharide-Induced Inflammatory Responses Through Inactivation of Mitogen-Activated Protein Kinase and Nuclear Factor-κB Signaling Pathway

Inflammation. 2016 Apr;39(2):583-91. doi: 10.1007/s10753-015-0283-1.

Abstract

Amomum tsao-ko (A. tsao-ko) has been used as a traditional medicine for the treatment of infectious and digestive disorders. In the present study, we report the anti-inflammatory activity and molecular mechanism of 2,8-decadiene-1,10-diol (DDO) isolated from the extract of A. tsao-ko in lipopolysaccharide-stimulated RAW 264.7 cells. DDO treatment inhibited the production of nitric oxide and prostaglandin E2 by downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression, respectively. Moreover, DDO suppressed the production of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. These inhibitory effects of DDO on the expression of inflammatory proteins were found to be mediated through the inactivation of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase and p38(MAPK), and inhibition of nuclear factor-κB (NF-κB) pathways including degradation of inhibitor of κB-α and nuclear localization of NF-κB. Taken together, these findings demonstrate the pharmacological roles and molecular mechanisms of DDO in regulating inflammatory responses, and suggest further evaluation and development of DDO as a potent therapeutic agent for the treatment of inflammatory disorders.

Keywords: 2,8-decadiene-1,10-diol; mitogen-activated protein kinases; nitric oxide; nuclear factor-κB; prostaglandin E2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amomum / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line, Transformed
  • Cyclooxygenase 2 / biosynthesis
  • Dinoprostone / biosynthesis
  • Down-Regulation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Fatty Alcohols / pharmacology*
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Interleukin-6 / biosynthesis
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lipopolysaccharides
  • Medicine, Korean Traditional
  • Mice
  • NF-KappaB Inhibitor alpha / metabolism*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / biosynthesis
  • Plant Extracts / pharmacology
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • 2,8-decadiene-1,10-diol
  • Anti-Inflammatory Agents
  • Fatty Alcohols
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dinoprostone