Comparative activities of daidzein metabolites, equol and O-desmethylangolensin, on bone mineral density and lipid metabolism in ovariectomized mice and in osteoclast cell cultures
Comparative activities of daidzein metabolites, equol and O-desmethylangolensin, on bone mineral density and lipid metabolism in ovariectomized mice and in osteoclast cell cultures
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DOI：
10.1007/s00394-008-0723-x
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发表时间：
2008-08-01
影响因子：
5
通讯作者：
Ishimi, Yoshiko
中科院分区：
文献类型：
--
作者：
Ohtomo, Takuya;Uehara, Mariko;Ishimi, Yoshiko
大豆苷元是大豆中的一种主要代谢产物，主要被人体肠道微生物代谢为雌马酚和O-去甲基安哥拉辛（O-DMA）。雌马酚具有比大豆黄酮更强的雌激素活性，然而，只有大约30%的人群被确定为雌马酚生产者，并且很少有直接证据表明另一种主要代谢产物O-DMA对雌激素缺乏状态的影响。因此，本研究的目的是比较O-DMA和雌马酚在体内和体外对骨和脂质代谢的影响。对于体内研究，将8周龄雌性小鼠分配到如下5组：假手术（sham）、卵巢切除（OVX）、OVX + 0.5 mg/天O-DMA（OVX + O-DMA）、OVX +0.5 mg/天雌马酚（OVX + Eq）和OVX + 0.03 μ g/天17 β-雌二醇（OVX + E2）给药。干预三周后，O-DMA和雌马酚没有影响OVX小鼠的子宫萎缩。OVX组股骨骨密度低于Sham组。雌马酚而不是O-DMA的管理，通过干预维持BMD。雌马酚和O-DMA处理的OVX小鼠的全身脂肪量和血脂值低于OVX小鼠。在体外研究中，在小鼠骨髓细胞与原代成骨细胞的共培养系统中，雌马酚以剂量依赖性方式显著抑制1 α，25（OH）（2）D-3诱导的破骨细胞形成。然而，O-DMA轻微抑制破骨细胞的形成，并且该作用不具有剂量依赖性。这些结果表明，O-DMA对OVX小鼠和破骨细胞培养的骨和脂质代谢的影响弱于雌马酚。
Daidzein, a major isoflavone predominantly found in soybean, is mainly metabolized to equol and O-desmethylangolensin (O-DMA) by the human gut microflora. Equol exhibits a stronger estrogenic activity than daidzein, however, only approximately 30% of the population has been identified as equol-producers and there are too few direct evidences of the effects of the other major metabolite, O-DMA on estrogen-deficient status. The purpose of this study is therefore, to compare the effect of both O-DMA and equol on bone and lipid metabolism in vivo and in vitro. For the in vivo study, 8-week-old female mice were assigned to five groups as follows: sham-operated (sham), ovariectomized (OVX), OVX + 0.5 mg/day O-DMA (OVX + O-DMA), OVX + 0.5 mg/day equol (OVX + Eq), and OVX + 0.03 mu g/day 17 beta-estradiol (OVX + E2) administration. Three weeks after the intervention, O-DMA and equol did not affect uterine atrophy in OVX mice. The bone mineral density (BMD) of the femur was lower in the OVX group than in the sham group. The administration of equol but not O-DMA, maintained BMD through the intervention. Values of whole body fat mass and plasma lipids were lower in the equol and O-DMA treated OVX mice than those in OVX mice. In the in vitro study, equol significantly inhibited the osteoclast formation induced by 1 alpha,25(OH)(2)D-3 in a dose-dependent manner in a co-culture system of mouse bone-marrow cells with primary osteoblastic cells. However, O-DMA slightly inhibited osteoclast formation, and the effect was not dose dependent. These results suggest that the effects of O-DMA on bone and lipid metabolism in OVX mice and osteoclast cell cultures are weaker than those of equol.