Structure-Activity Relationship of Anthocyanidins as an Inhibitory Effect on Osteoclast Differentiation

Hirata, Narumi; Tominari, Tsukasa; Ichimaru, Ryota; Taniguchi, Keita; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Ma, Sihui; Suzuki, Katsuhiko; Grundler, Florian M. W.; Miyaura, Chisato; Inada, Masaki

doi:10.1248/bpbreports.2.1_1

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“…The degradation of IκBα led to the inhibition of the NF-κB signaling pathway and the downregulation of osteoclast differentiation. Our previous reports also indicated that natural compounds, including nobiletin, delphinidin and β-cryptoxanthin, directly bound to IKKβ and inhibited the kinase activity of IKKβ [ 8 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of 4′-Demethylnobiletin and 4′-Demethyltangeretin on Osteoclast Differentiation In Vitro and in a Mouse Model of Estrogen-Deficient Bone Resorption

et al. 2023

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Citrus nobiletin (NOB) and tangeretin (TAN) show protective effects against disease-related bone destruction. We achieved demethylation of NOB and TAN into 4′-demethylnobiletin (4′-DN) and 4′-demethyltangeretin (4′-DT) using enzyme-manufacturing methods. In this study, we examined the effects of 4′-DN and 4′-DT on in vitro osteoclast differentiation, and on in vivo osteoporotic bone loss in ovariectomized (OVX) mice. 4′-DN and 4′-DT clearly suppressed the osteoclast differentiation induced by interleukin IL-1 or RANKL treatment. 4′-DN and 4′-DT treatments resulted in higher inhibitory activity in osteoclasts in comparison to NOB or TAN treatments. RANKL induced the increased expression of its marker genes and the degradation of IκBα in osteoclasts, while these were perfectly attenuated by the treatment with 4′-MIX: a mixture of 4′-DN and 4′-DT. In an in silico docking analysis, 4′-DN and 4′-DT directly bound to the ATP-binding pocket of IKKβ for functional inhibition. Finally, the intraperitoneal administration of 4′-MIX significantly protected against bone loss in OVX mice. In conclusion, 4′-DN, 4′-DT and 4′-MIX inhibited the differentiation and function of bone-resorbing osteoclasts via suppression of the NF-κB pathway. Novel 4′-DN, 4′-DT and 4′-MIX are candidates for maintaining bone health, which may be applied in the prevention of metabolic bone diseases, such as osteoporosis.

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Section: Discussionmentioning

confidence: 99%