摘要
目的:集成靶细胞捕集、液-质联用及分子对接技术研究藏药短管兔耳草调控尿酸转运体1(URAT1)成分及其与URAT1的结合机制,为基于藏族药短管兔耳草的降尿酸新药开发奠定物质与理论基础。方法:以可表达URAT1的HK-2细胞为靶细胞捕集藏族药短管兔耳草成分,运用超高压液相色谱飞行时间质谱(UPLC-Q-TOF-MS)技术对捕集成分进行鉴定,基于分子对接技术研究捕集成分与URAT1的结合机制。结果:HK-2细胞共捕集了短管兔耳草8个成分,经UPLC-Q-TOF-MS鉴定,分别为金丝桃甘、大车前苷、山柰酚-3-O-葡萄糖苷、黄大花洋地黄苷、假荆芥属苷、异黄大花洋地黄苷、高车前苷和木犀草素。分子对接结果显示这些成分可与URAT1通过氢键,范德华力,pi-pi作用和疏水作用等方式进行结合,但化合物与URAT1的结合机制和强弱,与化合物结构和类型密切相关。结论:靶细胞捕集,UPLC-Q-TOF-MS与分子对接集成技术可成功阐明藏族药短管兔耳草调控URAT1成分及成分与URAT1的结合机制,研究结果为基于藏族药短管兔耳草的降尿酸新药开发奠定一定的物质与理论基础。
Objective:To study the components with urate anion transporter 1(URAT1)regulation effect and their combination mechanisms of Lagotis brevituba by integrating techniques of HK-2 cell capture,UPLC-Q-TOF-MS and molecular docking,so as to provide material and theory bases for the development of new hypouricemic medicines based on L.brevituba.Method:The HK-2 cells were applied to capture the components of L.brevituba.UPLC-Q-TOF-MS was used to identify those components.The molecular docking technique was adopted to study the interaction mechanism between the compounds and URAT1.Result:Eight components were successfully screened and identified as hyperoside,plantamajoside,kaempferol-3-O-glucoside,lugrandoside,nepitrin,isolugrandoside,homoplantaginin,luteolin,respectively.Those components could combine with URAT1 mainly through hydrogen bond,van der Waals force and hydrophobic action,which were closely related to structure and compound types.Furthermore,the LibDock score of phenylethanoids was higher than that of flavonoids.Conclusion:The integration of target cell capture,UPLC-Q-TOF-MS and molecular docking techniques could be successfully used to identify captured compounds of L.brevituba with URAT1 regulation effects and illustrate their potential combination mechanisms as well as the structure-activity relationships.The findings may provide material and theory bases for the development of new hypouricemic medicines based on L.brevituba.
作者
任玲玲
毛竹
曾金祥
张迟
黄戎婕
张丽
周芳芳
朱玉野
李敏
梁健
朱继孝
钟国跃
REN Ling-ling;MAO Zhu;ZENG Jin-xiang;ZHANG Chi;HUANG Rong-jie;ZHANG Li;ZHOU Fang-fang;ZHU Yu-ye;LI Min;LIANG Jian;ZHU Ji-xiao;ZHONG Guo-yue(Research Center of Traditional Chinese Medicine(TCM)Resourcing and Minority Medicine,Jiangxi University of TCM,Nanchang 330004,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第17期119-125,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81660648)
江西省自然科学基金项目(20171BAB205090)
江西中医药大学民族药协同创新项目(JXXT2018001)
江西中医药大学研究生创新基金项目(JZYC18S11)。
