基于网络药理学和分子对接探讨补虚颗粒治疗产后贫血的作用机制

Mechanism of Buxu Granules in the Treatment of Postpartum Anemia Based on Network Pharmacology and Molecular Docking

目的 利用网络药理学和分子对接方法揭示补虚颗粒治疗产后贫血的物质基础及作用机制。方法 通过TCMSP、Swiss Target Prediction数据库分别获取补虚颗粒的化学成分以及相关靶点;通过GeneCards、OMIM、PubMed数据库获取产后贫血的相关靶点;利用Venny 2.1在线软件获取药物与疾病的共同靶点;由Cytoscape 3.8.2绘制药物-活性成分-靶点-疾病网络;STRING数据库构建蛋白质相互作用网络;通过DAVID数据库进行基因本体(GO)功能富集及京都基因与基因组百科全书(KEGG)通路富集分析;运用AutoDock软件对关键的活性成分和作用靶点进行分子对接验证。结果 补虚颗粒中44个有效成分通过调控137个靶点和103条通路治疗产后贫血,10个关键活性成分分别为华良姜素、山奈酚、常春藤皂苷元、甲基-11,14-二烯酸酯、异鼠李素、槲皮素、黄芩素、β-蜕皮甾酮、亚油酸乙酯、3,9-二-O-甲基尼森香豌豆紫檀酚,可通过TNF、IL-6、EGFR、MMP9、JUN、PTGS2、PPARG、HIF-1α、ESR1、CCND1等关键靶点介导癌症途径、糖尿病并发症中的AGE-RAGE、化学致癌作用与受体激活、钙离子、TNF、PI3K-Akt、HIF-1等信号通路发挥治疗产后贫血作用。分子对接表明,筛选的靶点蛋白与活性成分具有较好的结合能力。结论 该研究初步揭示了补虚颗粒发挥治疗产后贫血作用是通过多成分、多靶点、多途径实现的,从而为其分子机制的深入研究及临床应用提供思路。

Objective To predict the material basis and mechanism of Buxu granules in the treatment of postpartum anemia based on network pharmacology and molecular docking. Methods The chemical ingredients and corresponding targets of Buxu granules were collected by TCMSP and Swiss Target Prediction database. The postpartum anemia related targets were retrieved in GeneCards, OMIM, and PubMed database. Venny 2.1 online software was used to obtain the common targets of drugs-disease, and then the "drug-compound-target-disease" network diagram was constructed by using the software Cytoscape 3.8.2. The STRING database was used to draw the protein-protein interaction network, and the perform GO function and KEGG pathway enrichment analysis were carried out through DAVID database, and the AutoDock platform was applied in verifying the molecular docking of active components and core protein targets. Results The 44 active components of Buxu granules had the effect of treating postpartum anemia by regulating 137 targets and 103 pathways. Jaranol, kaempferol, hederagenin, methyl icosa-11,14-dienoate, isorhamnetin, quercetin, baicalein, β-ecdysterone, mandenol, and 3,9-di-O-methylnissolin were ten key compounds, which could mediate pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, chemical carcinogenesis-receptor activation, calcium, TNF, PI3K-Akt, HIF-1 and other signaling pathways through TNF, IL-6, EGFR, MMP9, JUN, PTGS2, PPARG, HIF-1α, ESR1, CCND1 and other key target proteins. The result of molecular docking showed that the targets and the components have a certain degree of binding. Conclusion This study preliminarily reveals that Buxu granules can treat postpartum anemia through multiple components, targets and pathways, which provides a reference for the further study of its molecular mechanism and clinical application.