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专家账号密码找回目的 基于中药复方专利用药规律，挖掘治疗脾虚湿蕴证溃疡性结肠炎（UC）的小复方，并通过网络药理学分析其潜在作用机制。方法 通过国家知识产权局官网检索治疗UC的中药复方专利，分析药物的药味、药性、归经、功效分类的频次、频率，并进行关联规则分析和聚类分析，挖掘治疗脾虚湿蕴证UC的小复方。通过中药系统药理学平台数据库和SwissADME数据库检索小复方药物的化学成分，利用SwissTargetPrediction 数据库预测化学成分的作用靶点，通过GeneCards®等数据库获取UC相关靶点，取两者交集作为潜在作用靶点。将潜在作用靶点导入STRING数据库，以Degree值排名前50的潜在作用靶点构建蛋白⁃蛋白相互作用网络，以与其相关联的化学成分作为潜在活性成分。对潜在作用靶点进行基因本体论功能富集分析和京都基因与基因组百科全书通路富集分析，通过Cytoscape软件构建药物⁃潜在活性成分⁃潜在作用靶点网络。结果 检索获得中药复方专利308项，包含525种药物，其中甘草、白术、黄连、白芍、木香、党参、茯苓、黄芪等药物的使用频次较高，525种药物以苦味、温性为主，多归脾经，以补虚药、清热药居多。关联规则分析结果显示，甘草、白术、白芍、茯苓、党参、木香、黄连等药物的关联性较强。聚类分析并结合临床经验得到治疗脾虚湿蕴证UC的小复方由白术、茯苓、党参、白芍、甘草、黄芪、木香组成。小复方的化学成分共149个，对应的作用靶点共1 008 个，UC相关靶点共1 918个，交集靶点（潜在作用靶点）共347 个，包括雌激素受体1（ESR1）、聚ADP核糖聚合酶1（PARP1）、前列腺素内过氧化物合酶2（PTGS2）等，潜在活性成分共105个，包括光甘草定、黄芪紫檀烷苷、美迪紫檀素等。富集分析结果显示，小复方治疗脾虚湿蕴证UC的作用靶点涉及蛋白质磷酸化、炎症反应、凋亡过程的负调节等生物过程，质膜及其成分、细胞质等细胞组分，ATP结合、蛋白丝氨酸/苏氨酸/酪氨酸激酶活性、蛋白激酶活性等分子功能，以及癌症通路、磷脂酰肌醇 3⁃激酶（PI3K）/蛋白激酶 B（AKT）信号通路、丝裂原活化蛋白激酶（MAPK）信号通路等信号通路。结论 从国家知识产权局官网中挖掘到治疗脾虚湿蕴证UC的小复方共包含7味药材，符合UC的临床治疗原则。潜在活性成分是光甘草定、黄芪紫檀烷苷、美迪紫檀素等，作用机制可能与其参与调控ESR1、PARP1、PTGS2等靶点，介导癌症通路、PI3K/AKT信号通路、MAPK信号通路等有关。
广西医学 页码：244-254
作者机构：覃淼，硕士，初级药师，研究方向为中药新药研究与开发。
基金信息：国家自然科学基金项目（81960872）；广西高校中青年教师科研基础能力提升项目（2024KY0314，2020KY43011）
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Objective To excavate the small complex prescriptions for the treatment of ulcerative colitis (UC) with syndrome of spleen deficiency and dampness accumulation based on medication rule of Traditional Chinese Medicine compound patents, and to analyze their potential mechanism through network pharmacology. Methods Traditional Chinese Medicine compound patents for the treatment of UC was retrieved from the official website of China National Intellectual Property Administration. The drug flavor, drug property, meridians, frequency of effect classification were analyzed, and the association rule analysis and cluster analysis were conducted for excavating small complex prescriptions for treating UC with syndrome of spleen deficiency and dampness accumulation. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissADME databases were adopted to search the chemical components of drugs of small complex prescriptions. The SwissTargetPrediction database was employed to predict effect targets of chemical components. The databases such as GeneCards® were used to obtain targets related to UC and intersection as potential effect targets. The potential effect targets were imported into the STRING database, and the top 50 potential effect targets with Degree value were used to establish a protein⁃protein interaction network, and the associated chemical components were used as potential active components. The Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on potential effect targets. The Cytoscape software was adopted to establish drug⁃potential active component⁃potential effect targets network. Results A total of 308 patents of Traditional Chinese Medicine compound were obtained, including 525 categories of drugs, among which drugs such as licorice, Atractylodes macrocephala, Coptidis rhizoma, Paeoniae radix alba, Aucklandiae radix, Codonopsis radix, Poria cocos, Hedysarum multijugum were frequently used. A total of 525 categories of drugs were mainly bitter and warm, mostly belonged to spleen meridian, and most of them were tonifying deficiency drugs and heat clearing drugs. The cluster analysis combined with clinical experience revealed that the small complex prescriptions for the treatment of UC with syndrome of spleen deficiency and dampness accumulation was composed of Atractylodes macrocephala, Poria cocos, Codonopsis radix, Paeoniae radix alba, licorice, Hedysarum multijugum, and Aucklandiae radix. There were 149 chemical components, 1008 corresponding effect targets, 1918 UC⁃related targets, and 347 intersection targets (potential targets) of the small complex prescriptions, including estrogen receptor 1 (ESR1), poly ADP ribose polymerase 1 (PARP1), prostaglandin endoperoxide synthase 2 (PTGS2), etc. A total of 105 potential active components were identified, including glabridin, astragalopteroside, and medipteroidin, etc. Enrichment analysis indicated that the effect targets of small complex prescriptions for the treatment of UC with syndrome of spleen deficiency and dampness accumulation were involved in biological processes such as protein phosphorylation, inflammatory response, and negative regulation of apoptosis, in cellular components such as plasma membrane and its components, cytoplasm, and in molecular functions such as ATP binding, protein serine/threonine/tyrosine kinase activity, and protein kinase activity, as well as in signaling pathways such as cancer pathway, phosphatidylinositol 3⁃kinase (PI3K)/protein kinase B (AKT) signaling pathway, mitogen⁃activated protein kinase (MAPK) signaling pathway. Conclusion The small complex prescriptions for the treatment of UC with syndrome of spleen deficiency and dampness accumulation excavated from the official website of China National Intellectual Property Administration contain 7 flavors of medicinal materials, which conforms to the clinical treatment principle of UC. The potential active components are glabridin, astragalopteroside, and medipteroidin, etc., and their mechanism may be related to their involvement in regulating targets such as ESR1, PARP1, PTGS2, mediating cancer pathway, PI3K/AKT signaling pathway, and MAPK signaling pathway.
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