Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-κB and AP-1 signaling pathways

Int Immunopharmacol. 2011 Sep;11(9):1166-72. doi: 10.1016/j.intimp.2011.03.014. Epub 2011 Mar 30.

Abstract

Angelica sinensis (AS), an herb used in traditional Chinese medicine, is thought to have anti-inflammatory activities. Ligustilide is its most abundant ingredient. This study sought to determine ligustilide's effects on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Ligustilide significantly suppressed the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α). The inhibition of NO was concomitant with a decrease in the protein and mRNA levels of LPS-induced nitric oxide synthase (iNOS). Furthermore, activation of activator protein-1 (AP-1) and nuclear factor κB (NF-κB) in the nucleus and the cytosolic degradation of IκBα were abrogated by ligustilide. Ligustilide also inhibited the phosphorylation of IκB kinase (IKK) and mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). The intracellular reactive oxygen species (iROS) level was also significantly decreased. These results suggest that ligustilide exhibits anti-inflammatory activities by blocking the activation of MAPKs/IKK and the downstream transcription factors AP-1 and NF-κB, which may result from ligustilide's down-regulation of iROS production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • Animals
  • Cell Line
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis
  • Down-Regulation / drug effects
  • I-kappa B Kinase / antagonists & inhibitors
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Kinase 4 / antagonists & inhibitors
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Macrophages / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Phosphorylation / drug effects
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor RelA / antagonists & inhibitors*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Transcription Factor AP-1
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • ligustilide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • I-kappa B Kinase
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Dinoprostone
  • 4-Butyrolactone