Poliothrysoside and its derivatives as novel insulin sensitizers potentially driving AMPK activation and inhibiting adipogenesis
Poliothrysoside and its derivatives as novel insulin sensitizers potentially driving AMPK activation and inhibiting adipogenesis
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DOI：
10.1016/j.ejmech.2014.09.015
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发表时间：
2014-10-30
影响因子：
6.7
通讯作者：
Gaikwad, Anil N.
中科院分区：
文献类型：
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作者：
Sashidhara, Koneni V.;Singh, Suriya P.;Gaikwad, Anil N.
在我们努力从自然界中开发安全和活性的化学实体的过程中，我们首先鉴定了poliothrysoside（1），一种从Flacourtia indica中分离的具有抗糖尿病潜力的植物成分。随后，合成了十五种衍生物（2-16）以评估这类化合物的活性特征。分析所有化合物在慢性胰岛素诱导的胰岛素抵抗3 T3-L1脂肪细胞中的葡萄糖摄取效力。有趣的是，化合物2表现出强烈的增加胰岛素敏感性的能力，主要激活AMPK信号通路，并且还以浓度依赖性方式抑制3 T3-L1脂肪细胞中的脂肪形成。总体而言，这些研究表明，poliothysoside及其衍生物作为非胰岛素依赖型2型糖尿病（T2 D）的有希望的线索的潜力。(C)2014年Elsevier Masson SAS。All rights reserved.
In our efforts to develop safe and active chemical entities from nature, we first identified poliothrysoside (1), a phytoconstituent isolated from Flacourtia indica, possessing antidiabetic potential. Subsequently, fifteen derivatives (2-16) were synthesized to assess the activity profile of this class. All the compounds were analyzed for their glucose uptake potency in chronic insulin-induced insulin resistant 3T3-L1 adipocytes. Interestingly, compound 2 exhibited strong ability to increase the insulin sensitivity, primarily activating the AMPK signaling pathway and also inhibited the adipogenesis in 3T3-L1 adipocytes, in concentration dependent manner. Overall, these studies suggest the potential of poliothrysoside and its derivatives as promising leads for non-insulin dependent type 2 diabetes (T2D). (C) 2014 Elsevier Masson SAS. All rights reserved.