Oral administration of phenolic antidiarrheic ingredients prevents ovariectomy-induced bone loss

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• 作者：Nobuaki Moriguchi ; Eiichi Hinoi ; Takeshi Takarada ; Nobuyuki Matsushima ; Kyosuke Uno ; Yukio Yoneda
• 关键词：Antidiarrheic ; Osteoclasts ; Osteoblasts ; Ovariectomy ; Bone loss
• 刊名：Biochemical Pharmacology
• 出版年：2007
• 期刊代码：2_00062952
• 类别：pha
• 出版时间：1 February 2007
• 卷：73
• 期：3
• 页码：385-393
• 文件大小：650 K

摘要

In the present study, we have attempted to evaluate the pharmacological actions of three major phenolic antidiarrheic ingredients, including 2-methoxyphenol (2MP), 2-methoxy-4-methylphenol (2M4MP) and 2-methoxy-4-ethyphenol (2M4EP), on the functionality and integrity of bone by in vitro and in vivo experimental techniques. Intermittent oral administration of 2M4MP and 2M4EP, but not 2MP, significantly prevented reductions of bone mineral density in total femur, distal femur and tibia, in addition to alterations of several osteoclastic parameters on histomorphometric analysis, when determined 28 days after ovariectomy in mice. All three phenolic ingredients examined significantly inhibited the developmental increase in the number of multinucleated cells positive to tartrate-resistant acid phosphatase staining in cultured mouse osteoclasts differentiated from bone marrow precursors in the presence of both macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand, which occurred in a concentration-dependent manner at a concentration range of 1 μM–1 mM without inducing cell death. Moreover, both 2M4MP and 2M4EP at 1 mM not only prevented the cell death induced by 0.5 mM H₂O₂ in cultured rat calvarial osteoblasts, but also suppressed the generation of intracellular reactive oxygen species in osteoblasts exposed to H₂O₂, with a radical scavenging action as revealed by electron spin resonance analysis. These results suggest that particular phenolic antidiarrheic ingredients may prevent ovariectomy-induced bone loss through a mechanism related to the inhibition of osteoclastogenesis in association with an anti-oxidative property in osteoblasts.