目的 通過網(wǎng)絡藥理學和分子對接技術探討土茯苓防治炎癥性腸病(IBD)的作用機制。方法 通過中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺(TCMSP)數(shù)據(jù)庫獲得土茯苓的活性成分;在TTD、OMIM、Gene Cards數(shù)據(jù)庫中去重、合并多平臺的IBD靶點信息;獲得活性成分和疾病靶點的交集并構建蛋白互作網(wǎng)絡圖(PPI)、“藥物-成分-靶點-疾病”互作網(wǎng)絡圖;利用Metascape數(shù)據(jù)庫對交集靶點進行基因本體(GO)富集分析和京都基因和基因組百科全書(KEGG)通路分析,獲得相關生物學過程信息及疾病作用通路;利用Cytoscape獲得核心靶點并使用AutoDock Tools 1.5.7對其進行分子對接。結果 共獲得15個活性成分、190個藥效成分靶點、2 171個疾病靶點,整理得到137個交集靶點,通過界值篩選得到28個核心靶點,其中5個為關鍵核心靶點,主要涉及P53核內(nèi)磷酸化蛋白(TP53)、白細胞介素-6(IL-6)、絲氨酸/蘇氨酸蛋白激酶1(AKT1)等,并推測磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信號通路是主要作用通路。分子對接結果顯示關鍵核心靶點與土茯苓相關活性成分具有關鍵的結合活性。結論 通過網(wǎng)絡藥理學初步揭示了土茯苓在防治炎癥性腸病方面的藥效成分、靶點及通路,為土茯苓應用于臨床治療IBD提供理論基礎。

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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國家自然科學基金資助項目(82204726);浙江中醫(yī)藥大學科研項目(2021RCZXZK16)