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

Sawako Moriwaki,Keiko Suzuki,Takeshi Into,Atsushi Nomura,Masashi Muramatsu,Fumihide Inoue,Yuji Yoshiko,Shumpei Niida,Mohan R Wani

doi:10.1371/journal.pone.0097177

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.

Highlights

Osteoporosis, characterized by low bone mineral density (BMD) and fragility of the bone matrix, is a complex bone disease with various causes, including aging, estrogen deficiency and genetics, and leads to increased fracture risk, especially in the elderly population
Effects of Anthocyanidins on Osteoclastogenesis to identify the active ingredients as antiosteoclastogenic factors, we investigated three major anthocyanidins, cyanidin, delphinidin and peonidin, which are commonly contained in many purple berries, including bilberry and blackcurrant (Figure 2A)
RAW264.7 cell cultures containing various concentrations of these anthocyanidins were incubated with soluble RANKL (sRANKL) (100 ng/ml) for 4 days

Summary

Introduction

Osteoporosis, characterized by low bone mineral density (BMD) and fragility of the bone matrix, is a complex bone disease with various causes, including aging, estrogen deficiency and genetics, and leads to increased fracture risk, especially in the elderly population. Current anti-osteoporosis drugs such as bisphosphonates have been widely used and their bone protective effects are well established. A subgroup of polyphenols including hesperidin, quercetin and luteolin, have been shown to possess preventive efficacy for bone loss in ovariectomized (OVX) animal models [6,7,8]. Most showed potent suppressive effects on the differentiation and/or function of osteoclasts, bone resorbing multinucleated giant cells [7,8,9,10]. Several flavonoids seem to be inhibitors of RANKL-RANK signaling-related molecules, including NF-kB and nuclear factor for activated T cells (NFATc1), master osteoclastogenic molecules located downstream of NF-kB [7,8,9,10]

Methods

Results

Conclusion