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二氢大豆苷元和 6-羟基大豆苷元介导发酵对去卵巢小鼠大豆抗骨质疏松作用的增强。

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

机构信息

Research Division of Food Functionality, Korea Food Research Institute, Wanju-gun, South Korea.

Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.

出版信息

FASEB J. 2019 Mar;33(3):3252-3263. doi: 10.1096/fj.201800953R. Epub 2018 Oct 30.

DOI:10.1096/fj.201800953R
PMID:30376359
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 anti-osteoporotic effect of soybeans in ovariectomized mice.

摘要

大豆的食用被认为对绝经后妇女的骨质疏松症有有益影响。然而,大豆发酵对生物利用度和抗骨质疏松作用的影响尚未阐明。为了解决这个问题,我们给去卵巢 C57BL/6J 小鼠喂食 5%的未发酵生大豆(RS)或发酵大豆(FS)补充饮食。经过 18 周的治疗,微计算机断层扫描显示 FSs 显著增加了骨矿物质密度,与 RSs 相比。这是因为骨形态发生蛋白 2(Bmp2)及其在骨组织中的下游靶标骨桥蛋白的上调。我们分析了 RS 或 FS 喂养的小鼠血清中的异黄酮代谢产物谱,并观察到 FS 喂养的小鼠血清中 19 种异黄酮代谢产物的水平显著升高。在这些代谢物中,我们观察到二氢大豆苷元(DHD)和 6-羟基大豆苷元(6-HD)都通过 Bmp2 信号通路增加了 MC3T3-E1 细胞中的成骨作用,并通过抑制 NF-κB 激活和 MAPK 磷酸化减少了 RAW264.7 细胞中核因子κ-B 配体诱导的破骨细胞生成。这些数据表明,FSs 的生物利用度提高是由于消费后产生了活性代谢物,如 DHD 和 6-HD。DHD 和 6-HD 可作为改善骨质疏松性骨丢失的潜在治疗药物。-金,J.-S.,李,H.,尼玛拉,F. S.,郑,C. H.,金,M. J.,张,Y.-J.,哈,T. Y.,安,J. Dihydrodaidzein 和 6-hydroxydaidzein 介导发酵诱导的大豆对去卵巢小鼠抗骨质疏松作用的增加。

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