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[《中医方剂大辞典》中“核心药物作用靶点”关联挖掘研究]

[Study on relevance mining of "core drug action target" in Dictionary of Traditional Chinese Medicine Prescriptions].

作者信息

Wang Bo, Zhou Rong-Rong, Tang Shi-Huan

机构信息

Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.

School of Basic Medical Sciences, Shanxi University of Traditional Chinese Medicine, Jinzhong 030600, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2018 Oct;43(19):3919-3926. doi: 10.19540/j.cnki.cjcmm.20180710.002.

Abstract

Based on the database of "Dictionary of Traditional Chinese Medicine Prescriptions", high-frequency herbs of Xiaoke disease is mined by traditional Chinese medicine inheritance support system, and core herbs and combinations are discovered through association rules and cluster analysis. On this basis, based on the integrative pharmacology of traditional Chinese medicine to explore the herb-disease relationship, the "herb-compound-target" network is constructed and enriched for the analysis of key target gene functions, metabolic pathways, and their "core herb-target interactions". In order to explore the molecular mechanism of its prevention and treatment of diabetes, 341 diabetes prescriptions are collected, organized, and tapped in the Dictionary of Traditional Chinese Medicine Prescriptions. Herb frequency statistics show that Licorice was the most commonly used, followed by Ophiopogonis Radix, Poria, Ginseng Radix et Rhizoma, Coptidis Rhizoma, etc., the medicinal properties are mostly cold, warm and ping, and the medicinal taste tends to be pungent, bitter, and sour, and they were attributed to lung meridian, stomach meridian, spleen meridian, etc. Among them, the 17 herbs were closely related. Ginseng Radix et Rhizoma, Ophiopogonis Radix, Poria and Glycyrrhizae Radix et Rhizoma were the core Chinese herbs. Ophiopogonis Radix was the key node of Coptidis Rhizoma, Trichosanthis Radix and core Chinese medicine, and Ophiopogonis Radix was the key node for the connection between Coptidis Rhizoma and Trichosanthis Radix and the core Chinese herbs. Using integrated pharmacology platform analysis, 10 crucial core targets for the prevention and treatment of diabetes were obtained, including the known disease targets (PLCD1, PIK3R1, ENPP1), and potential herb targets(GNB1, ADCY1, AKT1, RAC1, PRKAA1, RHOA) , common target (GCK). There were seven similar targets in the 10 crucial core targets predicted with the combination of "Ophiopogonis Radix, Coptidis Rhizoma and Trichosanthis Radix", including PLCD1, PIK3R1, ENPP1, ADCY1, AKT1, PRKAA1, GCK. These genes were mainly located in the cytosol, plasma membrane, etc., involved in adenosine triphosphate binding, protein binding, platelet activation, etc., mainly involved in the endocrine system, signal transduction, chemokine signaling pathway, cancer pathway, and other metabolic pathways, and it is speculated that these genes were potentially associated with diabetes. In this study, Traditional Chinese Medicine Inheritance Support System and Integrative Pharmacology of Traditional Chinese Medicine are used to analyze the prescription law of Xiaoke prescription, and the correlation of "core herbs-functionary targets" is excavated, which provided the basis and reference for the screening and development of TCM prescriptions for the prevention and treatment of diabetes.

摘要

基于《中药方剂大辞典》数据库,运用中医传承辅助系统挖掘消渴病高频用药,并通过关联规则和聚类分析发现核心药物及组合。在此基础上,基于中医整合药理学探索药物 - 疾病关系,构建并富集“药物 - 化合物 - 靶点”网络,分析关键靶基因功能、代谢通路及其“核心药物 - 靶点相互作用”。为探究其防治糖尿病的分子机制,收集、整理和挖掘《中药方剂大辞典》中341首糖尿病方剂。药物频次统计显示,甘草使用频次最高,其次为麦冬、茯苓、人参、黄连等,药性多为寒、温、平,药味多趋于辛、苦、酸,归经多为肺经、胃经、脾经等。其中,17味药物关联性密切,人参、麦冬、茯苓、甘草为核心中药。麦冬是黄连、天花粉与核心中药的关键节点,是连接黄连、天花粉与核心中药的枢纽。通过整合药理学平台分析,得到10个防治糖尿病关键核心靶点,包括已知疾病靶点(PLCD1、PIK3R1、ENPP1)、潜在药物靶点(GNB1、ADCY1、AKT1、RAC1、PRKAA1、RHOA)、共同靶点(GCK)。“麦冬、黄连、天花粉”组合预测的10个关键核心靶点中有7个相似靶点,包括PLCD1、PIK3R1、ENPP1、ADCY1、AKT1、PRKAA1、GCK。这些基因主要定位于胞质、质膜等,参与三磷酸腺苷结合、蛋白质结合、血小板活化等,主要涉及内分泌系统、信号转导、趋化因子信号通路、癌症通路等代谢途径,推测这些基因可能与糖尿病相关。本研究运用中医传承辅助系统和中医整合药理学分析消渴方剂用药规律,挖掘“核心药物 - 功能靶点”相关性,为筛选和研发防治糖尿病的中药方剂提供依据和参考。

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