Puerarin Exerted Anti-Osteoporotic Action Independent of Estrogen Receptor-Mediated Pathway
Puerarin Exerted Anti-Osteoporotic Action Independent of Estrogen Receptor-Mediated Pathway
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DOI：
10.3177/jnsv.58.202
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发表时间：
2012-06-01
影响因子：
1.6
通讯作者：
Kawamura, Yukio
中科院分区：
文献类型：
--
作者：
Michihara, Seiwa;Tanaka, Teruyoshi;Kawamura, Yukio
葛根素是一种大豆苷元 8-C 葡萄糖苷，是葛根 (Pueraria lobata) 中的主要异黄酮类化合物，其独特之处在于它在异黄酮类化合物结构的第 8 位含有 C-C 共轭葡萄糖。葛根素饮食以 5 mg/kg b.w./d 的剂量喂食卵巢切除小鼠 2 个月，可减少尿液中的脱氧吡啶啉（一种典型的骨降解产物）。由于葛根素喂养小鼠的骨吸收标志物、血清抗酒石酸酸性磷酸酶（TRAP）活性下降，但骨形成标志物、骨钙素水平没有改变，因此葛根素饮食被证明可以特异性抑制骨吸收，但不会抑制整体骨代谢。根据该结果，与未喂葛根素的小鼠相比，喂葛根素的小鼠的股骨结构得到了恢复。卵巢切除后因低雌激素（E2）水平而导致的萎缩子宫并不能通过葛根素饮食恢复，这表明葛根素在体内通过非雌激素受体（ER）介导的途径发挥抗骨质疏松作用。葛根素并未增强ER阳性人乳腺癌细胞MCF-70的生长，这表明葛根素对MCF-7细胞没有表现出雌激素样作用，即使浓度比E2高一万倍。此外，雌激素拮抗剂ICI182,780(Id)抑制E2促进的MCF-7细胞生长，但葛根素则不抑制MCF-7细胞的生长。在 ER 结合测定中，葛根素被证明不与 ER α 或 β 结合，或者说，即使是极弱的结合，尽管葛根素的苷元大豆黄酮与葛根素相比，显示出更强的结合。所有这些结果强烈表明葛根素发挥其抗骨质疏松作用不依赖于内质网介导的途径。
Puerarin, a daidzein-8-C glucoside, is the major isoflavonoid in Kudzu (Pueraria lobata), and is unique in that it contains C-C conjugated glucose at position 8 of the isoflavonoid structure. A puerarin diet at a dose of 5 mg/kg b.w./d to fed ovariectomized mice for 2 mo diminished the urinary deoxypyridinoline, a typical bone-degradation product. Since the bone absorption marker, serum tartarate-resistant acid phosphatase (TRAP) activity of puerarin-fed mice decreased but the bone formation marker, osteocalcin level, did not alter, the puerarin diet was proved to specifically depress the bone absorption, but not the overall bone metabolism. In accordance with that results, the femur structure of puerarin-fed mice was restored compared with that of puerarin-free diet mice. The atrophied uterine due to low estrogen (E2) level after ovariectomy was not restored by the puerarin diet, suggesting that puerarin exerted the anti-osteoporotic action through a non estrogen receptor (ER) mediated-pathway, in vivo. The growth of an ER-positive human breast cancer cell, MCF-70, was not enhanced by puerarin, suggesting that puerarin did not show estrogen-like action on MCF-7 cells, even at a ten thousand times higher concentration than that of E2. Furthermore, ICI182,780 (Id), an estrogen antagonist, suppressed the enhanced growth of MCF-7 cells by E2, but not that by puerarin. In an ER-binding assay, puerarin was proved not to bind to ER alpha or beta, or if all, extremely weakly, although daidzein, an aglycon of puerarin, showed a little stronger binding compared with puerarin. All these results strongly indicate that puerarin exerts its anti-osteoprotic action independently of the ER-mediated pathway.