基于指纹图谱、网络药理学预测黄芪“补气升阳”功效的质量标志物  

Quality markers for Astragalus membranaceus in tonifying qi and lifting yang based on fingerprint and network pharmacology

作　　者：王七龙 井亚江 黄建萍 王祥 安佳 王育朋 张岗 彭亮 高静 王昌利 颜永刚 WANG Qi-long;JING Ya-jiang;HUANG Jian-ping;WANG Xiang;AN Jia;WANG Yu-peng;ZHANG Gang;PENG Liang;GAO Jing;WANG Chang-li;YAN Yong-gang(Shaanxi University of Chinese Medicine/Shaanxi Qinling Application Development and Engineering Center of Chinese Herbal Medicine/Qin Medicine Research&Development Key Laboratory,Xianyang Shaanxi 712046;Shaanxi Haitian Pharmaceutical Co.,Ltd.,Xianyang Shaanxi 712000)

机构地区：[1]陕西中医药大学药学院/陕西省秦岭中草药应用开发工程技术研究中心/“秦药”研发重点实验室,陕西咸阳712046 [2]陕西海天制药有限公司,陕西咸阳712000

出　　处：《中南药学》2024年第6期1550-1557,共8页Central South Pharmacy

基　　金：陕西省中医药管理局专项项目:“第二批省级中医药中青年科技骨干人才项目”(No.2023-ZQNY-003);陕西中医药大学“秦药”品质评价与资源开发学科创新团队项目(No.2019-QN01);内蒙古自治区科技重大专项(No.2019ZD005)。

摘　　要：目的 基于HPLC-ELSD指纹图谱、网络药理学和分子对接技术预测黄芪“补气升阳”相关功效的质量标志物(Q-marker)。方法 针对黄芪“补气升阳”的功效进行药效学实验。应用HPLC-ELSD技术建立不同黄芪样品的指纹图谱,获取黄芪完整的化学成分信息。借助网络药理学研究技术手段,对多种数据库筛选得到的黄芪化学成分作用靶点与相关通路进行预测分析,构建蛋白互作网络、“成分-靶点-通路-疾病”图。使用分子对接技术将质量标志物与核心靶点进行对接验证,预测黄芪发挥“补气升阳”功效的成分。结果 药效学实验证明黄芪水煎液可下调机体丙二醛(MDA)、乳酸(LD)积累、肌酸激酶(CK)活力、肿瘤坏死因子α(TNF-α)水平;上调三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、脾脏指数、胸腺指数以达到补气、延缓疲劳、抗炎抗肿瘤等“补气升阳”类作用;黄芪指纹图谱指认了10个共有峰,结合网络药理学方法对候选化学成分进行分析,筛选获得14个核心靶点,20条代谢通路。分子对接结果显示,预测的质量标志物与靶标分子结合良好。结论 从质量标志物可测性和有效性的原则出发,结合药效学实验、指纹图谱、网络药理学、分子对接技术,将黄芪传统功效与现代疾病紧密联系对应,初步预测黄芪甲苷、毛蕊异黄酮葡萄糖苷、黄芪皂苷Ⅱ、黄芪皂苷Ⅲ、异黄芪皂苷Ⅰ这5种成分为黄芪发挥“补气升阳”功效的质量标志物。Objective To determine quality markers for Astragalus membranaceus tonifying qi and lifting yang based on HPLC-ELSD fingerprint network pharmacology and molecular docking.Methods Pharmacodynamic experiment was conducted.HPLC-ELSD was used to establish fingerprints of different Astragalus membranaceus samples and obtain the complete in Astragalus membranaceus chemical compositions information.With network pharmacology,the chemical targets and related pathways of Astragalus membranaceus were selected from various databases for analysis and established the protein interaction network and the composition-target-pathway-disease graph.Molecular docking was used to verify the quality markers and core targets,and to predict the components of Astragalus membranaceus in tonifying qi and lifting yang.Results Pharmacodynamic experiments showed that the decoction of Astragalus membranaceus down-regulated the levels of malondialdehyde,lactic acid accumulation,creatine kinase activity,and tumor necrosis factor-α,and up-regulated the levels of adenosine triphosphate,adenosine diphosphate,splenic index,and thymus index to tonifying qi and lifting yang,delay fatigue,and exert anti-inflammatory and anti-tumour effects.The fingerprint of Astragalus membranaceus identified 10 common peaks.Together with the network pharmacology,the candidate chemical components were analysed and screened to obtain 14 core targets and 20 metabolic pathways.The molecular docking showed that the predicted quality markers bound well to the target molecules.Conclusion Based on measurability and validity of quality markers,combining pharmacodynamic experiments,fingerprinting,network pharmacology,and molecular docking,we related the traditional efficacy of Astragalus membranaceus to modern diseases,and preliminarily predict that astragaloside,mauritian isoflavone glucoside,astragalosideⅡ,astragalosideⅢ,and isoastragalosideⅠ,are the five core chemical components of Astragaloside membranaceus.They tonifying qi and lifting yang through the modulation of

关 键 词：黄芪 质量标志物 指纹图谱 网络药理学 分子对接 药效学 

分 类 号：R284.1[医药卫生—中药学]