Delphinidin, one of the major anthocyanidins, prevents bone loss through the inhibition of excessive osteoclastogenesis in osteoporosis model mice

PLoS One. 2014 May 13;9(5):e97177. doi: 10.1371/journal.pone.0097177. eCollection 2014.

Abstract

Anthocyanins, one of the flavonoid subtypes, are a large family of water-soluble phytopigments and have a wide range of health-promoting benefits. Recently, an anthocyanin-rich compound from blueberries was reported to possess protective property against bone loss in ovariectomized (OVX) animal models. However, the active ingredients in the anthocyanin compound have not been identified. Here we show that delphinidin, one of the major anthocyanidins in berries, is a potent active ingredient in anti-osteoporotic bone resorption through the suppression of osteoclast formation. In vitro examinations revealed that delphinidin treatment markedly inhibited the differentiation of RAW264.7 cells into osteoclasts compared with other anthocyanidins, cyanidin and peonidin. Oral administration of delphinidin significantly prevented bone loss in both RANKL-induced osteoporosis model mice and OVX model mice. We further provide evidence that delphinidin suppressed the activity of NF-κB, c-fos, and Nfatc1, master transcriptional factors for osteoclastogenesis. These results strongly suggest that delphinidin is the most potent inhibitor of osteoclast differentiation and will be an effective agent for preventing bone loss in postmenopausal osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anthocyanins / administration & dosage
  • Anthocyanins / analysis
  • Anthocyanins / pharmacology*
  • Anthocyanins / therapeutic use
  • Blueberry Plants / chemistry*
  • Bone Resorption / prevention & control*
  • Cell Line
  • Female
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / drug effects
  • Osteoporosis / prevention & control*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • X-Ray Microtomography

Substances

  • Anthocyanins
  • NF-kappa B
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Proto-Oncogene Proteins c-fos
  • delphinidin

Grants and funding

This work has been supported by Japan Society for the Promotion of Science (KAKENHI Grant No. 20390469 to SN and No. 21791802 to SM) and by Ministry of Health Labour and Welfare (Health Labour Sciences Research Grant No. H24-Choju-007 to SN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.