The analgesic and anti-inflammatory effects of Litsea japonica fruit are mediated via suppression of NF-κB and JNK/p38 MAPK activation

Int Immunopharmacol. 2014 Sep;22(1):84-97. doi: 10.1016/j.intimp.2014.06.007. Epub 2014 Jun 23.

Abstract

Fruits of the Litsea family of trees and shrubs contain biologically active compounds, some of which have been used as natural nutrients and flavoring agents in food. In this study, we identified novel anti-nociceptive effects of the 30% ethanol extract, the CH(2)Cl(2) fraction and the associated active components (Hamabiwalactone A and B) from Litsea japonica fruit by using in vivo peripheral and central nervous pain models. In addition, we compared the anti-inflammatory effects of several fractions from L. japonica fruit extracts using lipopolysaccharide (LPS)-stimulated Raw264.7 cells. The CH(2)Cl(2) fraction of L. japonica fruit (LJM) had an optimal combination of anti-inflammatory effects and low cytotoxicity. Dose response studies were performed to determine the inhibitory effects of LJM on the pro-inflammatory enzymes, COX-2/PGE(2) and NO/iNOS, and pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α. Molecular profiling revealed that LJM exerts anti-inflammatory effects through inhibition of NF-κB and JNK/p38 MAPK signaling in LPS-induced macrophages. This study suggests that CH2Cl2 fraction of L. japonica fruit and its bioactive components are potential candidates as anti-inflammatory and analgesic agents (painkillers) for the treatment of inflammatory diseases.

Keywords: Analgesic; Anti-inflammatory; Cyclooxygenase-2; Hamabiwalactone; Litsea japonica.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives
  • 4-Butyrolactone / isolation & purification
  • 4-Butyrolactone / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Fruit
  • Furans / therapeutic use*
  • Humans
  • Immunosuppression Therapy
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / immunology
  • Litsea*
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Pain / drug therapy*
  • Pain / etiology
  • Phytotherapy*
  • Plant Extracts / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Furans
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • MAP Kinase Kinase 4
  • 4-Butyrolactone