Dihydrodaidzein and 6‐hydroxydaidzein mediate the fermentation‐induced increase of antiosteoporotic effect of soybeans in ovariectomized mice

Abstract

The consumption of soybeans is known to have beneficial effects on osteoporosis in postmenopausal women. However, the effects of soybean fermentation on the bioavailability and the antiosteoporotic effect have not yet been elucidated. To address this question, we fed ovariectomized C57BL/6J mice with a 5% nonfermented raw soybean (RS)‐ or fermented soybean (FS)‐supplemented diet. After 18 wk of treatment, microcomputed tomography showed that FSs significantly increased bone mineral density compared with RSs. This was because of the up‐regulation of bone morphogenic protein 2 (Bmp2) and its downstream target osteopontin in bone tissues. We analyzed isoflavone metabolite profiles in the sera of RS‐ or FS‐fed mice and observed that the levels of 19 isoflavone metabolites were significantly increased in the sera of FS‐fed mice. Among these metabolites, we observed that both dihydrodaidzein (DHD) and 6‐hydroxydaidzein (6‐HD) increased osteogenesis via Bmp2 signaling pathway in MC3T3‐E1 cells and reduced receptor activator of nuclear factor κ‐B ligand–induced osteoclastogenesis in RAW264.7 cells through the inhibition of NF‐κB activation and MAPK phosphorylation. These data suggest that improved bioavailability of FSs resulted from the production of active metabolites such as DHD and 6‐HD after consumption. DHD and 6‐HD can be used as potential therapeutics for the amelioration of osteoporotic bone loss.—Kim, J.‐S., Lee, H., Nirmala, F. S., Jung, C. H., Kim, M. J., Jang, Y.‐J., Ha, T. Y., Ahn, J. Dihydrodaidzein and 6‐hydroxydaidzein mediate the fermentation‐induced increase of antiosteoporotic effect of soybeans in ovariectomized mice. FASEB J. 33, 3252–3263 (2019). http://www.fasebj.org

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