Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum

Int Immunopharmacol. 2009 Oct;9(11):1272-80. doi: 10.1016/j.intimp.2009.07.011. Epub 2009 Aug 3.

Abstract

Ganoderma lucidum is a popular medicinal mushroom, which has been used in the Traditional Chinese medicine for the prevention or treatment of a variety of diseases. In the present study we evaluated the anti-inflammatory effects of the triterpene extract from G. lucidum (GLT) in LPS-stimulated macrophages. Here we show that GLT markedly suppressed the secretion of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and inflammatory mediator nitric oxide (NO) and prostaglandin E(2) (PGE(2)) from lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells. GLT also down-regulated LPS-dependent expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW264.7 cells. The anti-inflammatory effects of GLT were mediated by the inhibition of transcription factor NF-kappaB as demonstrated by decreased NF-kappaB-DNA binding activity, and the suppression of p65 phosphorylation in LPS-stimulated macrophages treated with GLT. Moreover, GLT inhibited LPS-dependent AP-1-DNA binding activity and down-regulated expression of AP-1 subunit c-Jun. In addition, GLT suppressed the activity of MAP kinases as observed by the down-regulation of LPS-induced phosphorylation of ERK1/2 and JNK but not p38. In vivo experiments clearly demonstrated that GLT also inhibited the production of TNF-alpha and IL-6 in LPS-induced endotoxemic mice. Apart from its anti-inflammatory activity, GLT suppressed cell proliferation of RAW264.7 cells through cell cycle arrest at G0/G1-G2M, which was mediated by the down-regulation of expression of cell cycle regulatory proteins cyclin D1, CDK4 and cyclin B1, respectively. In conclusion, the anti-inflammatory and anti-proliferative effects of GLT on macrophages are mediated through the inhibition of NF-kappaB and AP-1 signaling pathways.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • Reishi / chemistry
  • Triterpenes / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Drugs, Chinese Herbal
  • Inflammation Mediators
  • Lipopolysaccharides
  • Triterpenes