Delphinol®, a Delphinidin-Enriched Maqui Berry Extract, Improves Bone Metabolism through NF-κB Inactivation and Protects against Bone Loss in Osteopenic Mouse Models

We have reported that delphinidin, one of the most abundant anthocyanidins found in vegetables and berry fruits, inhibit osteoclast formation from RAW264.7 cells and prevent bone loss in mouse models of osteoporosis. To further confirm the bone protective effects of delphinidin, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. Delphinol® stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased osteoblastic marker alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that Delphinol® suppressed NF-κB nuclear translocation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, Delphinol® inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE 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 terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that Delphinol® can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation.