title: Oral administration of phenolic antidiarrheic ingredients prevents ovariectomy-induced bone loss.
abstract: 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-kappaB ligand, which occurred in a concentration-dependent manner at a concentration range of 1 microM-1mM without inducing cell death. Moreover, both 2M4MP and 2M4EP at 1mM not only prevented the cell death induced by 0.5mM 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.
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Moriguchi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hinoi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takarada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matsushima
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Uno
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D002478:Cells, Cultured; D003408:Cresols / Q000494:pharmacology*; D005260:Female; D006139:Guaiacol / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D053245:RANK Ligand / Q000494:pharmacology; D017382:Reactive Oxygen Species
chemical_list: D000930:Antidiarrheals; D000975:Antioxidants; D003408:Cresols; D053245:RANK Ligand; D017382:Reactive Oxygen Species; C505689:Tnfsf11 protein, mouse; D006139:Guaiacol; D016173:Macrophage Colony-Stimulating Factor; D006861:Hydrogen Peroxide; C025390:creosol