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

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

doi:10.3390/antiox8090386

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

Antioxidants (Basel). 2019 Sep 10;8(9):386. doi: 10.3390/antiox8090386.

Authors

Affiliations

¹ Department of Pharmacology, School of Dentistry, Ohu University, Fukushima 963-8611, Japan. m-nagaoka@den.ohu-u.ac.jp.
² Department of Oral Function and Molecular Biology, School of Dentistry, Ohu University, Fukushima 963-8611, Japan. t-maeda@den.ohu-u.ac.jp.
³ Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8551, Japan. chatani@dent.showa-u.ac.jp.
⁴ Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8551, Japan. kazuaki.handa@gmail.com.
⁵ Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8551, Japan. t.yamakawa@med.showa-u.ac.jp.
⁶ Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8551, Japan. skiyohara@dent.showa-u.ac.jp.
⁷ Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8551, Japan. koga@dent.showa-u.ac.jp.
⁸ Department of Oral Function and Molecular Biology, School of Dentistry, Ohu University, Fukushima 963-8611, Japan. yasumasa-kato@umin.ac.jp.
⁹ Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8551, Japan. takami@dent.showa-u.ac.jp.
¹⁰ Medical Genome Center, National Center for Geriatrics and Gerontology (NCGG), Aichi 474-8511, Japan. sniida@ncgg.go.jp.
¹¹ Anklam Extrakt GmbH, Marienbergstr. 92, 90411 Nuremberg, Germany. stefanie.lang@anklam-extrakt.com.
¹² School of Health Sciences, College of Health, Massey University, Palmerston North 4442, New Zealand. M.C.Kruger@massey.ac.nz.
¹³ Department of Pharmacology, School of Dentistry, Ohu University, Fukushima 963-8611, Japan. kei-suzuki@umin.ac.jp.

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.

Keywords: NF-κB; anthocyanin; antioxidant; delphinidin; maqui berry; osteoblast; osteoclast; osteopenic mouse; oxidative stress.