基于指纹图谱和网络药理学的经典名方三化汤质量标志物预测  

Prediction of Quality Markers of Classical Formula Sanhua Tang Based on Fingerprint and Network Pharmacology

作　　者：倪天婷 谈仲川 梅佳钰 罗鑫 朱靓婷 高洁 干国平 NI Tian-ting;TAN Zhong-chuan;MEI Jia-yu;LUO Xin;ZHU Liang-ting;GAO Jie;GAN Guo-ping(School of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Engineering Research Center for Traditional Chinese Medicine Processing,Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院,湖北武汉430065 [2]湖北省中药炮制工程技术研究中心,湖北武汉430065

出　　处：《中国现代中药》2024年第1期68-79,共12页Modern Chinese Medicine

基　　金：国家中医药管理局中药炮制技术传承建设项目(国中医药规财发[2015] 21号)。

摘　　要：目的:建立三化汤的指纹图谱,利用网络药理学方法筛选质量控制指标性成分。方法:建立15批三化汤的高效液相色谱法(HPLC)指纹图谱,采用“中药色谱指纹图谱相似度评价系统”(2012A版)进行相似度评价后确定共有峰;通过与对照药材、对照品比对,对峰进行归属和指认;并采用正交偏最小二乘法-判别分析(OPLS-DA)对15批三化汤进行质量评价;利用网络药理学筛选三化汤的核心作用靶点和通路,通过分子对接将核心靶点与13个成分进行对接验证,筛选出三化汤质量控制的指标性成分。结果:三化汤物质基准的HPLC指纹图谱共标定17个共有峰,相似度均大于0.97;共指认13个色谱峰,分别为辛弗林、柚皮苷、橙皮苷、新橙皮苷、芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚、厚朴酚、和厚朴酚、紫花前胡苷、异欧前胡素,其中含量排名前4的成分为柚皮苷、新橙皮苷、辛弗林、紫花前胡苷;OPLS-DA将样品分为3类,通过变量重要性投影得出新橙皮苷、柚皮苷、紫花前胡苷、大黄酸对三化汤物质基准影响较大;网络药理学预测13个成分可能通过肿瘤蛋白P53 (TP53)、蛋白激酶B1 (Akt1)、90 kDa热休克蛋白αA1 (HSP90AA1)、非受体酪氨酸激酶(SRC)、磷脂酰肌醇3-激酶催化亚基α (PIK3CA)等38个核心靶点,作用于内分泌抵抗、脂质和动脉粥样硬化、前列腺癌、PI3KAkt1信号通路、结直肠癌等157条主要通路发挥药效作用,度值前5位的成分为大黄素、大黄酚、大黄素甲醚、和厚朴酚、厚朴酚。分子对接结果显示,13个成分均能与Akt1稳定地结合。结论:通过整合含量测定、化学计量学、网络药理学,共筛选出新橙皮苷、柚皮苷、紫花前胡苷、大黄酸、辛弗林、大黄素、大黄酚、大黄素甲醚、和厚朴酚、厚朴酚10个成分可能为三化汤的质量标志物。Objective:To establish the fingerprints of Sanhua Tang and screen the quality control index ingredients by using the network pharmacology method.Methods:First,the HPLC fingerprints of 15 batches of Sanhua Tang were established,and the common peaks were identified after the similarity evaluation using the Chinese Medicine Chromatographic Fingerprints Similarity Evaluation System(version 2012A);then,the peaks were attributed and identified by comparing with the control herbs and the control products,and the quality evaluation of the 15 batches of Sanhua Tang was carried out by using the OPLS-DA method.Secondly,the core targets and pathways of Sanhua Tang were screened by using the network pharmacology method.Finally,the core targets were verified by molecular docking with 13 components,and the index components of Sanhua Tang were screened for quality control.Results:The HPLC fingerprints of the benchmarking of Sanhua Tang substances identified 17 common peaks with similarity greater than 0.97,and 13 chromatographic peaks were recognized,such as aloe-emodin,rhein,emodin,physcioner,chrysophanol,naringin,neohesperidin,hesperidin,synephrine,magnolol,honokiol,isoimperatorin,and nodakenin.Among them,the top four components were naringin,neohesperidin,synephrine,and nodakenin.The OPLS-DA classified the samples into three categories,and the variable importance projection showed that neohesperidin,naringin,nodakenin,and rhein had a greater impact on the benchmarking of Sanhua Tang substances.Network pharmacology predicted that the 13 active compounds might exert their pharmacodynamic effects through 38 core targets such as TP53,Akt1,HSP90AA1,SRC,PIK3CA,as well as 157 major pathways such as endocrine resistance,lipid and atherosclerosis,prostate cancer,colorectal cancer,and PI3K-Akt1 signaling pathway.The top five components were emodin,chrysophanol,physcioner,honokiol,and magnolol.The molecular docking results showed that 13 components could bind stably to the Akt1.Conclusion:By integrating content determination,chemometric

关 键 词：三化汤 经典名方 化学计量学 指纹图谱 网络药理学 

分 类 号：R284[医药卫生—中药学]