Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats
Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats
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DOI：
10.1016/j.jnutbio.2010.02.010
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发表时间：
2011-04-01
影响因子：
5.6
通讯作者：
Singh, Divya
中科院分区：
文献类型：
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作者：
Gautam, Abnish K.;Bhargavan, Biju;Singh, Divya
膳食大豆异黄酮包括染料木黄酮和大豆苷元已被证明在实验动物和人类雌激素缺乏期间具有有利的作用。我们已经评估了cladrin和芒柄花素的成骨作用，这两种结构相关的甲氧基大豆苷元在大豆食品和其他天然来源中发现。Cladrin，在低至10 nM，最大限度地刺激成骨细胞的增殖和分化，通过激活MEK-Erk途径。另一方面，芒柄花素在100 nM时最大程度地刺激成骨细胞分化，这涉及p38 MAPK通路，但对成骨细胞增殖没有影响。与大豆黄酮不同，这两种化合物既不激活成骨细胞的雌激素受体，也不影响破骨细胞的分化。对最近断奶的雌性Sprague-Dawley大鼠连续30天每日经口给予这些化合物中的每一种10.0 mg/kg（-1）日剂量，增加了所研究的各种解剖位置的骨矿物质密度。通过动态骨组织形态计量学，我们观察到，与对照组相比，用克拉德林治疗的大鼠表现出增加的矿物质沉积和骨形成率，而芒柄花素没有影响。与芒柄花素相比，克拉德林具有更好的血浆生物利用度。这些化合物均未在子宫内表现出雌激素激动作用。我们的数据表明，cladrin是更有效的促进峰值骨量的实现，这可能是由于其刺激成骨细胞增殖和更好的生物利用度的参数。据我们所知，这是第一次试图阐明甲氧基化大豆苷元与其成骨作用之间的构效关系。(C)2011 Elsevier Inc. All rights reserved.
Dietary soy isoflavones including genistein and daidzein have been shown to have favorable effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of cladrin and formononetin, two structurally related methoxydaidzeins found in soy food and other natural sources. Cladrin, at as low as 10 nM, maximally stimulated both osteoblast proliferation and differentiation by activating MEK-Erk pathway. On the other hand, formononetin maximally stimulated osteoblast differentiation at 100 nM that involved p38 MAPK pathway but had no effect on osteoblast proliferation. Unlike daidzein, these two compounds neither activated estrogen receptor in osteoblast nor had any effect on osteoclast differentiation. Daily oral administration of each of these compounds at 10.0 mg kg(-1) day(-1) dose to recently weaned female Sprague-Dawley rats for 30 consecutive days, increased bone mineral density at various anatomic positions studied. By dynamic histomorphometry of bone, we observed that rats treated with cladrin exhibited increased mineral apposition and bone formation rates compared with control, while formononetin had no effect. Cladrin had much better plasma bioavailability compared with formononetin. None of these compounds exhibited estrogen agonistic effect in uteri. Our data suggest that cladrin is more potent among the two in promoting parameters of peak bone mass achievement, which could be attributed to its stimulatory effect on osteoblast proliferation and better bioavailability. To the best of our knowledge, this is the first attempt to elucidate structure-activity relationship between the methoxylated forms of daidzein and their osteogenic effects. (C) 2011 Elsevier Inc. All rights reserved.