基于网络药理学和分子对接探讨多刺绿绒蒿中碎叶紫堇碱治疗氧化应激相关性疾病的作用机制  

Exploring the mechanism of action of cheilanthifoline from Meconopsis horridula in the treatment of oxidative stress-related diseases based on network pharmacology and molecular docking

作　　者：张琦 兰钧 阳勇 郭丽萍[3] 张小梅 达娃卓玛 王云红[1,2] 郭延垒 张成江 Zhang Qi;Lan Jun;Yang Yong;Guo Liping;Zhang Xiaomei;Dawa Zhuoma;Wang Yunhong;Guo Yanlei;Zhang Chengjiang(Analytical Chemistry Teaching and Research Office of the School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563099,China;Chongqing Institute of Traditional Chinese Medicine,Institute of Pharmaceutical Chemistry of Traditional Chinese Medicine,Nanan Chongqing 400065,China;Xizang Institute for Food and Drug Control,NMPA key Laboratory of Quality Control of Traditional Chinese Medicine and Tibetan Medicine,Lhasa Tibet 850000,China)

机构地区：[1]遵义医科大学药学院分析化学教研室,贵州遵义563099 [2]重庆市中药研究院中药药物化学研究所,重庆南岸400065 [3]西藏自治区食品药品检验研究院国家药品监督管理局中药(藏药)质量控制重点实验室,西藏拉萨850000

出　　处：《遵义医科大学学报》2023年第12期1161-1170,共10页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:21765027);国家重点研发计划项目(NO:2019YFC1712300);中国药品监管科学行动计划第二批重点项目(NO:NMPAJGKX-2023-082)。

摘　　要：目的检测多刺绿绒蒿中碎叶紫堇碱的含量并探索碎叶紫堇碱的抗氧化活性,利用网络药理学和分子对接技术探索碎叶紫堇碱通过抗氧化作用对治疗糖尿病(DM)、颅内动脉瘤(IA)、慢性阻塞性肺疾病(COPD)和动脉瘤性蛛网膜下腔出血(aSAH)的作用机制,为多刺绿绒蒿用于治疗氧化应激性相关疾病提供依据。方法采用高效液相色谱-质谱联用仪(HPLC-MS/MS)对多刺绿绒蒿中碎叶紫堇碱的含量进行测定;通过TLC-生物自显影法判定其抗氧化活性;使用SuperPred、Genecards和DisGeNET等在线数据库搜集碎叶紫堇碱的靶点和治疗DM、IA、COPD和aSAH的靶点,构建碎叶紫堇碱治疗疾病的“化合物-靶点-疾病”图和蛋白互作网络;基于Metascape数据库和CytoNCA插件进行KEGG通路富集分析;使用Discovery Studio 2019 Client软件对活性成分与潜在靶点进行分子对接验证结合活性。结果研究显示多刺绿绒蒿中碎叶紫堇碱的含量为0.1137μg/mL;TLC-生物自显影结果显示碎叶紫堇碱具有抗氧化活性;通过网络药理学分析获得碎叶紫堇碱治疗以上4种疾病的34个核心靶点;KEGG通路结果显示参与癌症途径、PI3K-Akt信号通路等118条KEGG通路;分子对接结果显示碎叶紫堇碱与SRC、RPS6KB1、ITGB1等蛋白结合稳定。结论多刺绿绒蒿中碎叶紫堇碱含量相对较高且通过多靶点、多途径发挥抗氧化的作用。Objective To detect the content of cheilanthifoline in Meconopsis horridula and explore the antioxidant activity of cheilanthifoline,and to explore the mechanism of action of cheilanthifoline through antioxidant action in the treatment of diabetes mellitus(DM),intracranial aneurysm(IA),chronic obstructive pulmonary disease(COPD),and aneurysmal subarachnoid hemorrhage(aSAH)by using web-based pharmacological and molecular docking techniques,which will provide a basis for the use of Meconopsis horridula in the treatment of oxidative stress-related diseases.Methods High-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)was used to determine the content of cheilanthifoline in Meconopsis horridula;The antioxidant activity was determined by TLC-bioautography;online databases,such as SuperPred,Genecards and DisGeNET,were used to collect the target sites of cheilanthifoline and those for the treatment of DM,IA,COPD and aSAH,so as to construct a“compound-target-disease”and protein-interaction network for the treatment of diseases with cheilanthifoline;KEGG pathway enrichment analysis was performed based on the Metascape database and CytoNCA plug-in;molecular docking of active ingredients with potential targets was performed to verify the binding activity using Discovery Studio 2019 Client software.Results The study showed that the content of cheilanthifoline in Meconopsis horridula was 0.1137μg/ml;TLC-bioautography showed that cheilanthifoline has antioxidant activity;34 core targets of cheilanthifoline for the treatment of the above four diseases were obtained by network pharmacological analysis;the results of the KEGG pathway showed that it was involved in 118 KEGG pathways such as cancer pathway,PI3K-Akt signaling pathway,and so on;and the results of molecular docking showed that cheilanthifoline bound stably to SRC,RPS6KB1,ITGB1 and other proteins.Conclusion The relatively high content of cheilanthifoline in Meconopsis horridula exerts antioxidant effects through multiple targets and pathways.

关 键 词：多刺绿绒蒿 TLC-生物自显影法 网络药理学 液相色谱-质谱联用仪 碎叶紫堇碱 

分 类 号：R285[医药卫生—中药学]