Fujioka Maiko, Uehara Mariko, Wu Jian, Adlercreutz Herman, Suzuki Kazuharu, Kanazawa Kazuki, Takeda Ken, Yamada Kazuhiko, Ishimi Yoshiko
Division of Applied Food Research, National Institute of Health and Nutrition, Tokyo, 162-8636, Japan.
J Nutr. 2004 Oct;134(10):2623-7. doi: 10.1093/jn/134.10.2623.
Soybean isoflavones have structures similar to that of estrogen and have received attention as alternatives to hormone replacement therapy for the prevention of postmenopausal osteoporosis. Daidzein, a major isoflavone found in soybean, is metabolized to equol by gut microflora, and the metabolite exhibits a stronger estrogenic activity than daidzein. However, there is no direct evidence that equol affects bone metabolism. In this study, we examined the effect of equol on the inhibition of bone loss in ovariectomized (OVX) mice. Female mice (8 wk old) were assigned to 5 groups as follows: sham-operated (sham), OVX, OVX + 0.1 mg/d equol administration (0.1 Eq), OVX + 0.5 mg/d equol administration (0.5 Eq), and OVX + 0.03 microg/d 17beta-estradiol administration (E(2)). Equol and E(2) were administered s.c., using a mini-osmotic pump. At 4 wk after the intervention, uterine weight was less in the OVX mice than in sham-operated mice (P < 0.05). The weight was maintained in the E(2) group. In contrast, administration of equol at doses used in this study did not affect uterine atrophy in OVX mice. Bone mineral density (BMD) for the whole body in the OVX group measured by dual-energy X-ray absorptiometry was lower than that in the sham group, whereas administration of 0.5 mg/d Eq as well as E(2) maintained the BMD. The BMD of the femur and lumbar spine in the OVX group was also lower than those in the sham group, and treatment with 0.5 mg/d Eq maintained it. Notably, the BMD of the proximal femur in the 0.5 Eq group was the same as that of the sham group. E(2) inhibited bone loss from all regions induced by OVX. These results suggest that equol, a major metabolite of daidzein, inhibits bone loss apparently without estrogenic activity in the reproductive organs of OVX mice.
大豆异黄酮具有与雌激素相似的结构，作为激素替代疗法的替代品用于预防绝经后骨质疏松症而受到关注。大豆苷元是大豆中发现的一种主要异黄酮，可被肠道微生物群代谢为雌马酚，且该代谢产物表现出比大豆苷元更强的雌激素活性。然而，尚无直接证据表明雌马酚会影响骨代谢。在本研究中，我们检测了雌马酚对去卵巢（OVX）小鼠骨丢失的抑制作用。将8周龄雌性小鼠分为5组如下：假手术组（sham）、OVX组、OVX + 0.1 mg/d雌马酚给药组（0.1 Eq）、OVX + 0.5 mg/d雌马酚给药组（0.5 Eq）以及OVX + 0.03 μg/d 17β-雌二醇给药组（E₂）。使用微型渗透泵皮下注射雌马酚和E₂。干预4周后，OVX小鼠的子宫重量低于假手术组小鼠（P < 0.05）。E₂组的子宫重量得以维持。相比之下，本研究中使用的剂量的雌马酚给药并未影响OVX小鼠的子宫萎缩。通过双能X线吸收法测量，OVX组的全身骨密度（BMD）低于假手术组，而0.5 mg/d Eq以及E₂给药可维持BMD。OVX组股骨和腰椎的BMD也低于假手术组，0.5 mg/d Eq治疗可维持其BMD。值得注意的是，0.5 Eq组股骨近端的BMD与假手术组相同。E₂抑制了OVX诱导的所有区域的骨丢失。这些结果表明，大豆苷元的主要代谢产物雌马酚在OVX小鼠的生殖器官中明显抑制骨丢失而无雌激素活性。
