目的: 研究课题组前期从藏药短管兔耳草中分离得到单体成分及松果菊苷与毛蕊花糖苷对黄嘌呤 氧化酶（XOD）的抑制活性,并探讨活性成分与 XOD 的结合机制,为基于藏药短管兔耳草的降尿酸新药开 发奠定物质基础。方法: 应用电化学生物传感法筛选 XOD 抑制活性成分,采用分子对接技术探讨活性成 分与 XOD 之间的结合机制,依据电化学生物传感信号分析藏药短管兔耳草的主要 XOD 抑制剂。结果: 21 个化合物中共筛选出 6 个 XOD 抑制剂,分别为毛蕊花糖苷、松果菊苷、兔耳草苷 H、6’-O-（4- 甲氧基 -（E）- 肉桂酰基）α/β- D- 吡喃葡萄糖苷、木犀草素和邻苯二甲酸二丁酯。其中,松果菊苷、兔耳草苷 H 与 6’-O-（4- 甲氧基 -（E）- 肉桂酰基）α/β- D- 吡喃葡萄糖苷为从藏药短管兔耳草中新发现的 XOD 抑 制剂,松果菊苷与毛蕊花糖苷为藏药短管兔耳草中主要 XOD 抑制剂成分。除邻苯二甲酸二丁酯抑制活性-1较弱外,其余 5 个成分的 XOD 抑制活性均较强,IC50 值介于 3.28~7.56 mg·L-1 之间。这些活性成分通过 氢键、范德华力、pi-pi 作用和疏水作用等方式与 XOD 进行结合。结论: 研究为基于藏药短管兔耳草 XOD 抑制剂类降尿酸新药的开发奠定了一定的物质基础,电化学生物传感方法与分子对接技术联用为中草药 XOD 抑制剂的活性与机制研究提供了一种新的工具。
Objective: To study the xanthine oxidase（XOD）inhibitory activities of the components obtained from Lagotis brevituba Maxim in our previous work as well as echinacoside and verbascoside,and the binding mechanisms between the active compounds and XOD. The aim for these works is to lay the material bases for development of new drugs with hypouricemia effect based on L. brevituba Maxim. Methods: The electrochemical biosensing method was applied to study the inhibitory activities of components on XOD,the molecular docking method was selected to study the binding mechanisms between the active compounds and XOD,the electrochemical biosensing signals of the compounds and extract were compared to speculate the main XOD inhibitors of L. brevituba Maxim. Results: 6 Components from 21 possessed XOD inhibitory activities,which were luteolin,verbascoside, echinacoside,6-p-coumaroylsucrose,6’-O-（4-methoxy-trans-cinnamoyl）a/β-D -glucpyranose and dibutyl phthalate. Among them,echinacoside,lagotoside H and 6’-O-（4-methoxy-trans-cinnamoyl）a/β-D- glucopyranose were XOD inhibitors reported for the first time in this work. However,the main XOD inhibitors of L. brevituba Maxim were echinacoside and verbascoside. The dibutyl phthalate showed weak XOD inhibitory activities, while other 5 XOD inhibitors possessed strong XOD inhibitory activities with IC50 values ranging from 3.28 to 7.56 mg·L-1. The results of molecular docking showed that these active compounds combinded with XOD mainly through hydrogen bonding,van der Waals force,pi - pi interaction and hydrophobic interaction. Conclusions: The study laid a material base for development of new drugs with hypouricemia effect based on inhibitors of L. brevituba Maxim．The electrochemical biosensing and molecular docking methods provided a new tool for research of XOD inhibitors of traditional Chinese medicine.
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