Construction of Fe3O4@α-glucosidase magnetic nanoparticles for ligand fishing of α-glucosidase inhibitors from a natural tonic Epimedii Folium
Construction of Fe3O4@α-glucosidase magnetic nanoparticles for ligand fishing of α-glucosidase inhibitors from a natural tonic Epimedii Folium
复制标题
Fe3O4@α-葡萄糖苷酶磁性纳米颗粒的构建，用于从天然补品淫羊藿叶中捕获α-葡萄糖苷酶抑制剂的配体
DOI：
10.1016/j.ijbiomac.2020.10.018
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发表时间：
2020-12-15
影响因子：
8.2
通讯作者：
Jia, Xiaobin
中科院分区：
文献类型：
--
作者：
Shen, Yuping;Wang, Man;Jia, Xiaobin
抑制α-葡萄糖苷酶活性是治疗2型糖尿病的有效方法。淫羊藿叶是α-葡萄糖苷酶抑制剂(AGIs)的重要来源，但其生物活性成分和药理机制尚不清楚。在这项研究中，建立了一种新的策略，利用α-葡萄糖苷酶功能化的磁珠来筛选潜在的AGI，然后用UPLC-MS/MS分析它们。此外，还利用分子对接技术预测了AGIs与酶的结合模式，并估算了IC50值。经响应面优化后，α-葡萄糖苷酶在pH 6.81的磷酸盐缓冲液中固定化4.22h，Fe3O4@α-葡萄糖苷酶活力最高，并从淫羊藿叶提取物中分离出8种黄酮类化合物，经体外抑制实验和分子对接进一步确定为淫羊藿苷A、淫羊藿苷B、淫羊藿苷A、箭舌草苷B、2“-O-鼠李糖苷淫羊藿苷II和保活草苷I。其中，保火苷I和箭毒皂苷B的抑制活性强于阿卡波糖。该方法在方便地筛选针对各种受体的生物活性化合物方面具有重要的应用前景，为从天然产物中开发新药提供了一个有效的平台。(C)2020爱思唯尔B.V.保留所有权利。
Inhibition of alpha-glucosidase activity is an effective way for treatment of type 2 diabetes mellitus. Epimedii Folium is an important source of alpha-glucosidase inhibitors (AGIs), however bioactive compounds and pharmacological mechanisms remained unclear. In this study, a novel strategy was established, which harnessed alpha-glucosidase functionalized magnetic beads to fish out potential AGIs, followed by UPLC-MS/MS analysis for their identification. Furthermore, molecular docking was employed to predict binding patterns between the AGIs and the enzyme, and IC50 values was estimated as well. After response surface methodology optimization, the highest activity of Fe3O4@alpha-glucosidase has been achieved when 1.17 mg/mL of alpha-glucosidase was immobilized in phosphate buffer (pH 6.81) for 4.22 h. Moreover, eight flavonoids were fished out from the extract of Epimedii Folium, and then identified to be epimedin A, epimedin B, epimedin C, icariin, sagittatoside A, sagittatoside B, 2"-O-rhamnosyl icariside II and baohuoside I. All of them were further confirmed to be AGIs through in vitro inhibitory assay and molecular docking. Among those, baohuoside I and sagittatoside B possessed stronger inhibitory activity than acarbose. The approach has a significant prospect in conveniently screening bioactive compounds that target various receptors, which provided an efficient platform for new drug development from natural products. (C) 2020 Elsevier B.V. All rights reserved.