(S)-雌马酚比(R)-雌马酚更能有效地抑制破骨细胞形成和增强破骨细胞凋亡，并减少去势小鼠的雌激素缺乏性骨丢失。

(S)-Equol Is More Effective than (R)-Equol in Inhibiting Osteoclast Formation and Enhancing Osteoclast Apoptosis, and Reduces Estrogen Deficiency-Induced Bone Loss in Mice.

机构信息

Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.

Department of Health and Nutrition, Faculty of Human Sciences, Hokkaido Bunkyo University, Eniwa, Japan.

出版信息

J Nutr. 2022 Aug 9;152(8):1831-1842. doi: 10.1093/jn/nxac130.

DOI:10.1093/jn/nxac130

PMID:35675296

Abstract

BACKGROUND

Equol, a metabolite of daidzein, binds to the estrogen receptor with greater affinity than daidzein and exhibits various biological properties. It exists as an enantiomer, either (S)-equol or (R)-equol.

OBJECTIVES

We have previously shown that the inhibitory effect of (S)-equol on bone fragility is stronger than that of racemic equol in ovariectomized (OVX) mice; however, the effect of (R)-equol has not been elucidated. The aim of this study was to compare the activities of equol enantiomers on bone metabolism in vitro and in vivo.

METHODS

Bone marrow cells (BMCs) and RAW 264.7 cells were treated with equol enantiomers. The number of osteoclasts and caspase-3/7 activity were measured. We examined the effect of equol enantiomers on osteoblast differentiation in MC3T3-E1 cells. In vivo, 8-wk-old female ddY mice were assigned to 4 groups: sham-operated (sham), OVX, OVX + 0.5 mg/d of (S)-equol (S-eq), and OVX + 0.5 mg/d of (R)-equol (R-eq). Four weeks after the intervention, femoral bone mineral density (BMD) and osteoclastic gene expression were analyzed, along with concentrations of equol enantiomers in the serum and tissues.

RESULTS

(S)-equol and (R)-equol inhibited osteoclast differentiation in BMCs (97% and 60%, P < 0.05) and RAW 264.7 cells (83% and 68%, P < 0.05). (S)-equol promoted apoptosis of mature osteoclasts by inducing caspase-3/7 activity (29%, P < 0.05) and enhanced osteoblast differentiation (29%, P < 0.05). In OVX mice, BMD was ameliorated in (S)-equol-treated mice (11%, P < 0.05), but not in (R)-equol-treated mice. The concentrations of (S)-equol were greater than those of (R)-equol in the serum, tibia, liver, and kidney (by 148%, 80%, 22%, and 139%, respectively).

CONCLUSIONS

These results suggest that (S)-equol is more effective than (R)-equol in inhibiting osteoclast formation and enhancing osteoclast apoptosis in vitro, supporting the beneficial effect of (S)-equol to reduce estrogen deficiency-induced bone loss in OVX mice.

摘要

背景

黄豆苷元的代谢产物雌马酚与雌激素受体的亲和力大于黄豆苷元，并表现出各种生物学特性。它以对映异构体（S）-雌马酚或（R）-雌马酚的形式存在。

目的

我们之前已经表明，（S）-雌马酚对去卵巢（OVX）小鼠骨脆性的抑制作用强于外消旋雌马酚；然而，（R）-雌马酚的作用尚未阐明。本研究旨在比较雌马酚对映异构体在体外和体内对骨代谢的活性。

方法

用雌马酚对映异构体处理骨髓细胞（BMCs）和 RAW 264.7 细胞。测量破骨细胞的数量和 caspase-3/7 活性。我们研究了雌马酚对映异构体对 MC3T3-E1 细胞成骨分化的影响。在体内，将 8 周龄雌性 ddY 小鼠分为 4 组：假手术（sham）、OVX、OVX+0.5mg/d（S）-雌马酚（S-eq）和 OVX+0.5mg/d（R）-雌马酚（R-eq）。干预 4 周后，分析股骨骨密度（BMD）和破骨细胞基因表达，以及血清和组织中雌马酚对映异构体的浓度。

结果

（S）-雌马酚和（R）-雌马酚抑制 BMCs（97%和 60%，P<0.05）和 RAW 264.7 细胞（83%和 68%，P<0.05）中的破骨细胞分化。（S）-雌马酚通过诱导 caspase-3/7 活性（29%，P<0.05）和增强成骨细胞分化（29%，P<0.05）促进成熟破骨细胞凋亡。在 OVX 小鼠中，（S）-雌马酚处理小鼠的 BMD 得到改善（11%，P<0.05），但（R）-雌马酚处理小鼠则没有。血清、胫骨、肝脏和肾脏中（S）-雌马酚的浓度大于（R）-雌马酚（分别为 148%、80%、22%和 139%）。