Methoxylated Isoflavones, Cajanin and Isoformononetin, Have Non-Estrogenic Bone Forming Effect Via Differential Mitogen Activated Protein Kinase (MAPK) Signaling
Methoxylated Isoflavones, Cajanin and Isoformononetin, Have Non-Estrogenic Bone Forming Effect Via Differential Mitogen Activated Protein Kinase (MAPK) Signaling
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DOI：
10.1002/jcb.22264
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发表时间：
2009-10-01
影响因子：
4
通讯作者：
Chattopadhyay, Naibedya
中科院分区：
文献类型：
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作者：
Bhargavan, Biju;Gautam, Abnish Kumar;Chattopadhyay, Naibedya
在从Butea monosperma的茎皮提取物中获得的铅之后，研究了两种结构上相关的甲氧基异黄酮;木豆素和异芒柄花素在成骨细胞中的作用。Cajanin对成骨细胞具有强烈的促有丝分裂和促进分化作用，这涉及随后的MEK-Erk和Akt通路的激活。另一方面，异芒柄花素表现出强大的抗凋亡作用，除了促进成骨细胞分化，涉及MEK-Erk和Akt途径的平行激活。与染料木黄酮或大豆苷元不同，这两种化合物似乎都不通过成骨细胞中的雌激素受体起作用。对最近断奶的雌性Sprague-Dawley大鼠每日一次经口（灌胃）给药，连续30天，每种化合物的剂量为10.0 mg/kg（-1）/天（-1）。与对照组相比，Cajanin增加了所有骨骼部位的骨密度（BMD）、骨生物力学强度、矿物质沉积率（MAR）和骨形成率（BFR）。与对照组相比，异芒柄花素也增加了不同解剖位置的BMD水平，但其效果不如木豆素。与对照组相比，异芒柄花素虽然提高了MAR和BFR，但对骨生物力学强度参数没有影响。异芒柄花素有非常轻微的子宫增重作用，而木豆素没有任何这种作用。我们的数据表明，木豆素是更有效的比异芒柄花素在加速峰值骨量的实现。据我们所知，这项工作代表了第一次试图阐明两个甲氧基化的甾体酮之间的构效关系，关于它们在成骨细胞和骨形成的影响。J.细胞。108：388-399，2009. (C)2009威利-利斯公司
Following a lead obtained from stem-bark extract of Butea monosperma, two structurally related methoxyisoflavones; cajanin and isoformononetin were studied for their effects in osteoblasts. Cajanin had strong mitogenic as well as differentiation-promoting effects on osteoblasts that involved subsequent activation of MEK-Erk and Akt pathways. On the other hand, isoformononetin exhibited potent antiapoptotic effect in addition to promoting osteoblast differentiation that involved parallel activation of MEK-Erk and Akt pathways. Unlike genistein or daidzein, none of these two compounds appear to act via estrogen receptors in osteoblast. Once daily oral (by gavage) treatment for 30 consecutive days was given to recently weaned female Sprague-Dawley rats with each of these compounds at 10.0 mg kg(-1) day(-1) dose. Cajanin increased bone mineral density (BMD) at all skeletal sites studied, bone biomechanical strength, mineral apposition rate (MAR) and bone formation rate (BFR), compared with control. BMD levels at various anatomic positions were also increased with isoformononetin compared with control however, its effect was less potent than cajanin. Isoformononetin had no effect on the parameters of bone biomechanical strength although it enhanced MAR and BFR compared with control. Isoformononetin had very mild uterotrophic effect, whereas cajanin was devoid of any such effect. Our data suggest that cajanin is more potent than isoformononetin in accelerating peak bone mass achievement. To the best of our knowledge, this work represents the first attempt to elucidate structure-activity relationship between the two methoxylated isoflavones regarding their effects in osteoblasts and bone formation. J. Cell. Biochem. 108: 388-399, 2009. (C) 2009 Wiley-Liss, Inc.