Delphinidin, one of the most abundant anthocyanidins found in vegetables and berry fruits, has been reported to inhibit the formation of osteoclasts from RAW264.7 cells and prevent bone loss in osteoporosis mouse models. We investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo to further support the bone protective effects of delphinidin. By upregulating bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA, Delphinol® stimulated the osteoblastic differentiation of MC3T3-E1 cells, as demonstrated by increased mineralized nodule formation and increased osteoblastic marker alkaline phosphatase activity. Immunostaining and immunoprecipitation assays showed that by functioning as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells, Delphinol ® inhibited NF-aB nuclear translocation. Delphinol® simultaneously prevented both osteoclastogenesis in primary bone marrow macrophages and pit formation on dentine slices by matured osteoclasts. Microcomputed tomography (micro-CT) and femoral bone histomorphometry analysis showed that regular MBE ingestion significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminal ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (ratio of bone formation to tissue volume), and signified BFR/TV (rate of bone formation to tissue volume) (trabecular separation), Compared to the vehicle controls in the osteopenic mouse models, ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclasts per unit of bone surface). These results indicate that by not only inhibiting bone resorption but also promoting bone development, Delphinol® may be a promising natural agent for the prevention of bone loss in osteopenic conditions.
Author (s) DetailsKeiko Suzuki
Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8555, Japan.
Masahiro Nagaoka
Department of Pharmacology, School of Dentistry, Ohu University, Fukushima 963-8611, Japan.
Shumpei Niida
Research Institute, National Center for Geriatrics and Gerontology (NCGG), Aichi 474-8511, Japan.
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