基于网络药理学及数据挖掘探讨中药调节铁死亡的用药规律研究

Study on Medication Rules of Herbs in the Regulation of Ferroptosis Based on Network Pharmacology and Data Mining

关键词:  铁死亡  网络药理学  用药规律  物质基础  中药开发

Key words:  ferroptosis  network pharmacology  medication rule  material basis  Chinese medicine development

摘要:

目的 探讨中药干预铁死亡的物质基础及用药规律。方法 通过整合人类基因数据库（Genecard）、基因组百科全书数据库（KEGG）获取铁死亡的作用靶点，以类药性≥ 0.18为条件，在中药系统药理学技术平台中筛选出可作用于靶点的化合物及中药，并构建靶点-化合物、化合物-中药、靶点-化合物-中药网络。借助在线分子对接平台（Systems Dock Web Site）将度值前4的靶点与候选化合物进行分子对接，以验证预测结果及进一步挖掘潜在的化合物靶点组合。通过查询各中药的性味归经等信息，对中药进行规律分析。结果 共获得65个铁死亡的作用靶点，15个可匹配到候选化合物的靶点，收集到35个候选化合物，301味中药；分子对接结果显示，化合物-靶点网络中涉及的药物靶点结合活性较佳，并挖掘出与度值前4靶点相关的潜在新组合72个，其中3个对接得分高于化合物-靶点网络已有组合。频数统计结果显示，可干预铁死亡的中药药味以苦、辛为主，药性以寒居多，主要归肝、肺二经。结论 本研究较系统地探讨了中药干预铁死亡的物质基础，总结了铁死亡相关中药的一般规律，为今后的中西医结合临床及开发铁死亡干预药物提供了思路。

Abstract:

OBJECTIVE To analyze the material basis and rule of herbs in the regulation of ferroptosis. METHODS The target of ferroptosis was collected by integrating the Kyoto encyclopedia of genes and genomes database(KEGG) and Genomes human gene database(Genecards), the ingredient and herbs of traditional Chinese medicine system pharmacology platform was selected by the use of druglike ≥ 0.18. The target-compound network, as well as compound-herbs and target-compound-herbs network were constructed. Docking between targets that degree ranked top 4 and candidate compounds was performed by the online molecular docking platform(Systems Dock Web Site) to verify the relationship of target-compound network and further exploit the new compound target combinations. By querying the information of the property and flavor to analyzing the rules of all herbs. RESULTS A total of 65 targets for ferroptosis were obtained. Fifteen targets were matched to compounds, 35 candidate compounds and 301 herbs were collected. Molecular docking results showed that the binding activity in the compound-target network was better. There were 72 potential drug-targets relationships that associated with the top 4 targets of the degree, and there were 3 combinations of docking scores over the compound-target network. Frequency statistics found that the traditional Chinese medicine which could interfere with ferroptosis was mainly bitter and acrid, distribute to liver, lung channel. CONCLUSION This study systematically analyzes the material molecules of Chinese medicine intervention for ferroptosis, summarized the general rules of herbs, and provides ideas for clinical application of integrated Chinese and western medicine and the drugs development of ferroptosis intervention.