基于电化学生物传感与分子对接技术研究短管兔耳草成分对XOD的抑制活性及其结合机制  

Study on xanthine oxidase inhibitors and their binding mechanisms of Lagotis Brevituba maxim based on electrochemical biosensing and molecular docking methods

作　　者：毕莹 任玲玲 毛竹 曾金祥 张迟 熊浩仲 李敏 梁健 朱继孝 钟国跃 BI Ying;REN Ling-ling;MAO Zhu;ZENG Jin-xiang;ZHANG Chi;XIONG Hao-zhong;LI Min;LIANG Jian;ZHU Ji-xiao;ZHONG Guo-yue(Nanchang Hongdu Hospital of TCM,Nanchang 330006,China;The Research Center of Chinese Medicine Resource and National Medicine of Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]南昌市洪都中医院,南昌330006 [2]江西中医药大学中药资源与民族药研究中心,南昌330004

出　　处：《药物分析杂志》2021年第6期953-961,共9页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金(81660648);江西省教育厅基金(GJJ201227);江西中医药大学民族药协同创新项目(JXXT2018001);江西中医药大学中药双一流学科建设项目(JXSYLXK-ZHYAO033)。

摘　　要：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-Dglucopyranose 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.

关 键 词：短管兔耳草 降尿酸 电化学生物传感 分子对接 黄嘌呤 氧化酶 抑制剂 

分 类 号：R917[医药卫生—药物分析学]