Gambogic acid inhibits osteoclast formation and ovariectomy-induced osteoporosis by suppressing the JNK, p38 and Akt signalling pathways

Biochem J. 2015 Aug 1;469(3):399-408. doi: 10.1042/BJ20150151. Epub 2015 Jun 11.

Abstract

Excessive osteoclast formation and bone resorption are key causes of osteoporosis. Natural compounds can serve as alternative therapeutic agents for the prevention and treatment of osteoporosis, and some natural compounds may have advantages over traditional drugs. In the present paper, we report that the natural compound GBA (gambogic acid), which is bioavailable, effective and less toxic, inhibits osteoclast formation, thereby attenuating osteoclastic bone resorption in vitro. Further in vivo studies demonstrated that GBA prevented ovariectomy-induced bone loss in a dose-dependent manner. Moreover, we demonstrated that GBA suppressed RANKL (receptor activator of nuclear factor κB ligand)-induced JNK (c-Jun N-terminal kinase), p38 and Akt phosphorylation. Taken together, our results demonstrate that GBA inhibits osteoclast formation in vitro and in vivo, suggesting that it is of potential value in the treatment of osteoclast-related diseases.

Keywords: Akt; JNK; gambogic acid; osteoclasts; osteoporosis; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / enzymology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Humans
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Protein v-akt / genetics
  • Oncogene Protein v-akt / metabolism*
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Osteoclasts / enzymology
  • Osteoporosis / drug therapy*
  • Osteoporosis / enzymology*
  • Osteoporosis / etiology
  • Osteoporosis / genetics
  • Ovariectomy / adverse effects*
  • RANK Ligand / metabolism
  • Signal Transduction / drug effects
  • Xanthones / administration & dosage*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • RANK Ligand
  • Xanthones
  • gambogic acid
  • Oncogene Protein v-akt
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4