Prunin is a highly potent flavonoid from Prunus davidiana stems that inhibits protein tyrosine phosphatase 1B and stimulates glucose uptake in insulin-resistant HepG2 cells
Prunin is a highly potent flavonoid from Prunus davidiana stems that inhibits protein tyrosine phosphatase 1B and stimulates glucose uptake in insulin-resistant HepG2 cells
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DOI：
10.1007/s12272-016-0852-3
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发表时间：
2017-01-01
影响因子：
6.7
通讯作者：
Choi, Jae Sue
中科院分区：
文献类型：
--
作者：
Jung, Hyun Ah;Ali, Md. Yousof;Choi, Jae Sue
Prunin 是山桃茎中的主要黄酮类化合物，可改善链脲佐菌素诱导的糖尿病大鼠的高血糖和高脂血症。本研究的目的是通过抑制蛋白酪氨酸磷酸酶 1B (PTP1B)、α-葡萄糖苷酶、过氧亚硝酸盐 (ONOO-) 介导的酪氨酸硝化以及刺激胰岛素抵抗肝细胞中的葡萄糖摄取，研究李子素的体外抗糖尿病潜力。此外，还进行了分子对接模拟来预测 PTP1B 抑制期间的特定普鲁宁结合模式。 Prunin 对 PTP1B 显示出很强的抑制活性，IC50 值为 5.5 +/- 0.29 A mu M，对 α-葡萄糖苷酶具有显着的抑制活性，IC50 值为 317 +/- 2.12 A mu M。此外，动力学研究表明，prunin 抑制 PTP1B (K (i) = 8.66) 和 α-葡萄糖苷酶 (K (i) = 189.56）分别具有竞争型和混合型抑制剂的典型特征。对接模拟表明，Prunin 通过靶向 PTP1B 的活性位点选择性抑制 PTP1B，并表现出良好的结合亲和力，对接分数为 -9 kcal/mol。此外，李宁对 ONOO 介导的酪氨酸硝化表现出剂量依赖性抑制活性，并通过降低胰岛素抵抗 HepG2 细胞中 PTP1B 的表达水平来刺激葡萄糖摄取。这些结果表明，李宁具有作为选择性 PTP1B 抑制剂的巨大潜力，并且可能通过改善胰岛素抵抗而具有抗糖尿病特性。
Prunin is the main flavonoid in Prunus davidiana stems and improves hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. The aim of this study was to investigate the in vitro anti-diabetic potential of prunin via the inhibition of protein tyrosine phosphatase 1B (PTP1B), alpha-glucosidase, peroxynitrite (ONOO-)-mediated tyrosine nitration, and stimulation of glucose uptake in insulin-resistant hepatocytes. In addition, a molecular docking simulation was performed to predict specific prunin binding modes during PTP1B inhibition. Prunin showed strong inhibitory activity against PTP1B, with an IC50 value of 5.5 +/- 0.29 A mu M, and significant inhibitory activity against alpha-glucosidase, with an IC50 value of 317 +/- 2.12 A mu M. Moreover, a kinetics study revealed that prunin inhibited PTP1B (K (i) = 8.66) and alpha-glucosidase (K (i) = 189.56) with characteristics typical of competitive and mixed type inhibitors, respectively. Docking simulations showed that prunin selectively inhibited PTP1B by targeting its active site and exhibited good binding affinity, with a docking score of -9 kcal/mol. Furthermore, prunin exhibited dose-dependent inhibitory activity against ONOO--mediated tyrosine nitration and stimulated glucose uptake by decreasing PTP1B expression level in insulin-resistant HepG2 cells. These results indicate that prunin has significant potential as a selective PTP1B inhibitor and may possess anti-diabetic properties by improving insulin resistance.