加味柴胡疏肝汤君臣配伍抗癫痫作用机制的网络药理学和分子对接研究

Research on the Mechanism of the Compatibility of Monarch and Ministerial Drug in Modified Chaihu Shugan Tang in the Treatment of Epilepsy Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学方法探讨加味柴胡疏肝汤中君药和臣药配伍的抗癫痫作用机制,并通过分子对接技术预测药物有效成分与抗癫痫靶标的结合性。方法:从DisGeNET和GeneCards数据库中分别收集癫痫的靶标,取二者交集。在TCMSP数据库中检索加味柴胡疏肝汤中君药和臣药的有效成分及靶标。利用在线软件Venny进行映射得到加味柴胡疏肝汤君臣配伍抗癫痫作用的潜在靶标。通过STRING数据库构建基因功能关联网络。基于clusterProfiler包进行GO富集分析(gene ontology,GO)和KEGG富集分析(kyoto encyclopedia of genes and genomes,KEGG)。同时使用Cytoscape软件构建“成分-靶标-通路”关系网络。最后,通过Autodock Vina实现君臣配伍有效成分与癫痫靶标蛋白的分子对接。结果:加味柴胡疏肝汤君臣配伍的多种有效成分能够作用于癫痫的37个潜在靶标。这些潜在靶标主要影响了69个GO生物学功能。涉及了113条KEGG信号通路。此外,加味柴胡疏肝汤君臣配伍的有效成分均可与癫痫核心靶标自发地结合,且结合性良好。结论:加味柴胡疏肝汤君臣配伍的有效成分与癫痫相关的靶标具有良好的结合性。加味柴胡疏肝汤君臣配伍的有效成分可能是通过多靶标、多途径共同发挥抗癫痫作用的。

Objective: To discuss the mechanism of the compatibility of monarch and ministerial drug in modified Chaihu Shugan Tang in treating epilepsy, and predict the binding of active ingredients to antiepileptic targets through molecular docking technology. Methods: The targets of epilepsy were collected from DisGeNET and GeneCards databases, and their intersection was used as targets related to epilepsy. The active ingredients and the targets of monarch and ministerial drug in modified Chaihu Shugan Tang were searched from TCMSP. Online software Venny was used for mapping to obtain the potential targets of antiepileptic effects of the compatibility of monarch and ministerial drug in modified Chaihu Shugan Tang. STRING database was used to construct gene function association network, clusterProfiler pack was used to perform GO and KEGG. Meanwhile, Cytoscape software was used to build the relation network of "ingredient-targets-pathway". Consequently, Autodock Vina was used to realize molecular docking between the active ingredients of the compatibility of monarch and ministerial drug and target proteins of epilepsy. Results: Multiple active ingredients of the compatibility of monarch and ministerial drug in modified Chaihu Shugan Tang could act on 37 potential targets of epilepsy. These potential targets mainly affect 69 GO biological function, and involve 113 KEGG signaling pathway. Besides, the active ingredients of the compatibility of monarch and ministerial drug in modified Chaihu Shugan Tang could combine with core targets of epilepsy spontaneously, presenting good combination. Conclusion: Active ingredients of the compatibility of monarch and ministerial drug in modified Chaihu Shugan Tang have good combination with the epilepsy-related targets, which could possibly develop antiepileptic effects through many targets and pathways.