Kobophenol A enhances proliferation of human osteoblast-like cells with activation of the p38 pathway

Int Immunopharmacol. 2013 Nov;17(3):704-13. doi: 10.1016/j.intimp.2013.08.015. Epub 2013 Sep 7.

Abstract

Bone cell proliferation, bone formation, and bone resorption are the main factors involved in the homeostasis of the bone mass. Osteoblast death is a problem experienced by postmenopause women. Herbal medicines have attracted considerable attention for use as a drug or a drug substitute in the treatment of bone-related diseases, such as osteoporosis. This study investigated the effects of kobophenol A on the proliferation in human osteoblast cells. Kobophenol A stimulated the proliferation of osteoblast cells by the increases in DNA synthesis and the enhancement of cell cycle progression. Kobophenol A stimulation induced the expression of the cyclin B1 and cyclin-dependent kinase 1 (CDK1). Treatment of osteoblast cells with p38 MAPK inhibitor SB203580 significantly inhibited kobophenol A-enhanced proliferation. In addition, kobophenol A induced phosphorylation of p38 MAPK. Treatment of osteoblast cells with kobophenol A resulted in improvement of ROS scavenging activity. Moreover, kobophenol A treatment up-regulated the Bcl-2 level, but down-regulated the level of Bax expression. We also demonstrate that kobophenol A increased alkaline phosphatase (ALP) activity after 2 days. Taken together, the results of this study reveal that kobophenol A has proliferative effects and enhances ALP activity in osteoblast cells and these findings provide insights into the development of a therapeutic approach of kobophenol A in the prevention of osteoporosis and other bone disorders.

Keywords: Kobophenol A; Osteoblast; Proliferation; ROS; p38 MAPK.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Bone Density Conservation Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Humans
  • Nitric Oxide / metabolism
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Stilbenes / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Bone Density Conservation Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Stilbenes
  • kobophenol A
  • Nitric Oxide
  • p38 Mitogen-Activated Protein Kinases
  • Alkaline Phosphatase