A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models.

Masahiro Nagaoka,Masahiro Chatani,Stefanie Lang,Masamichi Takami,Shumpei Niida,Takako Negishi-Koga,Keiko Suzuki,Tomoyuki Yamakawa,Marlena Kruger,Toyonobu Maeda,Yasumasa Kato,Shuichi Kiyohara,Kazuaki Handa

doi:10.3390/antiox8090386

Abstract

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased 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 MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE 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 MBE 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.

Highlights

Osteoporosis is a common disease characterized by decreased bone mass and impairment of the skeletal architecture, resulting in an increased frequency of fracture
Tb.Sp, ES/BS and N.Oc/BS, compared to vehicle controls in osteopenic mouse models. These findings suggest that maqui berry extract (MBE) can be a promising natural agent for the prevention of bone loss in osteopenic conditions by inhibiting bone resorption, and stimulating bone formation
Delphinol® is standardized to contain a minimum of 25% delphinidins and a minimum of 35% total anthocyanins, resulting in an exceptionally high antioxidant capacity assayed by oxygen radical absorbance capacity (ORAC) test system

Summary

Introduction

Osteoporosis is a common disease characterized by decreased bone mass and impairment of the skeletal architecture, resulting in an increased frequency of fracture. Osteoporosis occurs in more than 30% of postmenopausal women [1], and is strongly associated with diminishing estrogen levels. It is well recognized that a decline in estrogen levels impacts on the differentiation and activity of osteoclasts (OC) and osteoblasts (OB), enhancing the rate of activation and resulting in an imbalance between bone resorption and bone formation, leading to decreased bone mass [2]. In addition to this, increased oxidative stress has been shown to be the key mechanism leading to bone loss seen in the elderly, in both men and women [6,7,8]. Osteoporosis is known to be one of the chronic lifestyle-related diseases

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