The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low succe...The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low success rates and high attrition of drug candidates1. The current methodology of new drug R&D is deeply influenced by the idea of allopathic medicine, which directly inhibits biological targets.展开更多
目的运用数据挖掘与网络药理学方法,系统分析中药治疗心功能不全的组方用药规律及其潜在机制,为中医药干预心功能不全提供理论依据与研究思路。方法检索中国知网、万方数据知识服务平台、维普网、中国生物医学文献数据库、Web of Scienc...目的运用数据挖掘与网络药理学方法,系统分析中药治疗心功能不全的组方用药规律及其潜在机制,为中医药干预心功能不全提供理论依据与研究思路。方法检索中国知网、万方数据知识服务平台、维普网、中国生物医学文献数据库、Web of Science核心合集数据库、Pub Med、Embase及Cochrane Library中英文数据库,收集建库至2025年1月公开发表的中医药治疗心功能不全的相关方剂文献,筛选后构建方剂数据库。利用古今医案云平台(V2.3.7)进行数据挖掘,提取药物四气、五味、归经,药物使用频次及配伍规律等核心观察指标;结合传统中医药系统药理学数据库与分析平台、本草组鉴数据库及相关文献筛选核心方药及其活性成分,并通过SwissTargetPrediction等工具预测药物靶点。联合Gene Cards、OMIM、Drug Bank、TTD数据库获取心功能不全疾病相关靶点,筛选共同靶点并构建“中药-成分-靶点-疾病”网络,采用Cytoscape3.10.2构建蛋白质-蛋白质相互作用(PPI)网络,通过Metascape平台开展基因本体(GO)和京都基因和基因组数据库(KEGG)富集分析,并采用分子对接方法验证核心成分与关键靶点的结合活性。结果共纳入228首方剂,涵盖218味中药,用药以温、平、微寒为主,药味多为甘、辛、苦,归经主要集中于肺、心经和脾经。常见功效包括生津养血、利水消肿、活血祛瘀等。其中“黄芪→丹参”的共现频率最高,黄芪、丹参、附子、茯苓、麦冬、炙甘草为高频药物,构成核心处方。网络药理学分析共筛选得104个活性成分,969个作用靶点,与疾病相关重叠靶点354个。PPI网络分析筛选出10个核心靶点基因,分别为Akt1、TNF、BCL2、CASP3、ESR1、STAT3、MMP9、PTGS2、IL-6和JUN。GO富集分析显示,这些靶点主要参与细胞运动调控、激素应答与循环系统过程等生物过程。KEGG通路富集分析揭示其显著富集于TNF、MAPK、m TOR、VEGF等信号通路。分子对接结果提示,关键化合物对核心靶点有良好结合活性。结论中医药治疗心功能不全的组方用药整体体现出“益气活血、温阳利水”的基本规律。核心成分可能通过多靶点、多通路协同作用干预细胞凋亡、心肌重构等关键病理过程,从而发挥综合治疗效应,为中医药防治心功能不全提供潜在机制依据。展开更多
文摘The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low success rates and high attrition of drug candidates1. The current methodology of new drug R&D is deeply influenced by the idea of allopathic medicine, which directly inhibits biological targets.
