目的 通过网络药理学和分子对接技术探讨土茯苓防治炎症性肠病(IBD)的作用机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)数据库获得土茯苓的活性成分;在TTD、OMIM、Gene Cards数据库中去重、合并多平台的IBD靶点信息;获得活性成分和疾病靶点的交集并构建蛋白互作网络图(PPI)、“药物-成分-靶点-疾病”互作网络图;利用Metascape数据库对交集靶点进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路分析,获得相关生物学过程信息及疾病作用通路;利用Cytoscape获得核心靶点并使用AutoDock Tools 1.5.7对其进行分子对接。结果 共获得15个活性成分、190个药效成分靶点、2 171个疾病靶点,整理得到137个交集靶点,通过界值筛选得到28个核心靶点,其中5个为关键核心靶点,主要涉及P53核内磷酸化蛋白(TP53)、白细胞介素-6(IL-6)、丝氨酸/苏氨酸蛋白激酶1(AKT1)等,并推测磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路是主要作用通路。分子对接结果显示关键核心靶点与土茯苓相关活性成分具有关键的结合活性。结论 通过网络药理学初步揭示了土茯苓在防治炎症性肠病方面的药效成分、靶点及通路,为土茯苓应用于临床治疗IBD提供理论基础。

Objective To discuss the mechanism of Smilax glabra in treatment of inflammatory bowel disease based on network pharmacology and molecular docking technology.Methods The active components of S. glabra were obtained from TCMSP database. Deduplicating and merging IBD target information of multiple platforms in TTD, OMIM and Gene Cards databases. Obtain the intersection of active components and targets and construct PPI network diagram and “drug-component-target-disease” interaction network diagram. The GO enrichment analysis and KEGG pathway analysis of intersection targets were carried out by using Metascape database, and the relevant biological process information and disease pathway were obtained. Using Cytoscape to obtain core target and molecular docking with Auto Dock Tools 1.5.7.Results A total of 15 active components, 190 active component targets and 2 171 disease targets were obtained, 137 intersection targets were sorted out, and 28 core targets were screened by boundary value, of which 5 were key core targets, mainly involving TP53, IL-6, and AKT1. It is speculated that PI3K/Akt signal pathway is the main action pathway. The results of molecular docking showed that the key core targets had key binding activity with the active components related to S. glabra.Conclusion The active ingredients, targets and pathways of S. glabra in prevention and treatment of inflammatory bowel disease were preliminarily revealed through network pharmacology, which provides a theoretical basis for the clinical application of S. glabra in the clinical treatment of IBD.

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国家自然科学基金资助项目(82204726);浙江中医药大学科研项目(2021RCZXZK16)