Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum

Eur J Pharmacol. 2009 Jan 5;602(1):1-7. doi: 10.1016/j.ejphar.2008.11.005. Epub 2008 Nov 9.

Abstract

The preventative effects of the ethanol extracts of Ganoderma lucidum against the ovariectomized (Ovx)-induced deterioration of bone density in 11-week-old female Sprague Dawley (SD) rats were investigated. The results showed that the G. lucidum-treated Ovx rats showed improved bone density compared with the Ovx rats. We studied the effects of G. lucidum on osteoclastic differentiation using bone marrow cells and RAW 264 cell D-clone (RAW-D). Differentiation, in response to receptor activator of NF-kappaB ligand (RANKL) and a tumor necrosis factor alpha (TNF-alpha), was inhibited by the ethanol extracts of G. lucidum and ganoderic acid DM which was isolated as one of the active compounds by bioassay-guided fractionation. Ganoderic acid DM especially suppresses the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). This suppression leads to the inhibition of dendritic cell-specific transmembrane protein (DC-STAMP) expression and reduces osteoclast fusion.

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Cell Differentiation / drug effects*
  • Cell Fusion
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects
  • Ovariectomy
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RANK Ligand / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Reishi / chemistry*
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Membrane Proteins
  • NFATC Transcription Factors
  • Plant Extracts
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • ganoderic acid D
  • ganoderic acid Me