基于网络药理学探讨葛根解酒的作用机制

Exploring the Mechanism of Gegen Hangover Based on Network Pharmacology

摘要: 目的：运用网络药理学的方法，预测葛根的活性成分和作用靶点，揭示葛根解酒的分子作用机制。方法：通过中药系统药理学数据库(TCMSP)检索葛根中所含的全部化学成分，以ADME参数(OB ≥ 30%和 DL ≥ 0.15)，筛选具有活性的化学成分，并查找活性化学成分对应的靶点蛋白，建立靶点数据集；使用Cytoscape3.6.1软件构建“活性成分–靶点–疾病”复杂网络关系图；通过生物学信息注释数据库(DAVID)进行GO生物功能富集分析和KEGG通路富集分析，探明葛根解酒的作用机制。结果：共检索出18个化合物，其中4个化学成分为活性化合物；共检索出92个作用靶点。通过网络拓扑特征评价，筛选出8个潜在作用靶点与葛根解酒的作用机制最为密切；利用DAVID数据库对潜在作用靶点进行基因GO功能富集分析和KEGG通路富集分析，筛选出35个生物过程和28条信号通路参与葛根解酒的作用。其中与葛根解酒较为密切的信号通路包括神经活性配体–受体相互作用、钙信号途径、胆碱能突触、心肌细胞中的肾上腺素信号、PI3K-AKT信号通路、VEGF信号通路、p53信号通路、NAFLD等信号通路，同时其主要涉及的生物过程包括雌二醇反应、突触传递、胆碱能、腺苷酸环化酶抑制G蛋白偶联乙酰胆碱受体信号通路、磷脂酶C激活G蛋白偶联乙酰胆碱受体信号通路、γ-氨基丁酸信号通路、RNA聚合酶II启动子转录的阳性调控作用、细胞色素c激活参与凋亡过程的半胱氨酸型内肽酶活性等，从而发挥多成分、多靶点、多途径解酒的生物学效应。结论：网络药理学为葛根解酒的作用机制提供了研究方向及科学依据。

Abstract: Objective: To predict the active constituents and targets of Radix Puerariae by using network pharmacology, and to reveal the molecular mechanism of Gegen hangover. Methods: All the chemical components contained in Radix Puerariae were searched by the Chinese Medicine System Pharmacology Database (TCMSP). The active chemical constituents were screened by ADME parameters (OB ≥ 30% and DL ≥ 0.15), and the target proteins corresponding to the active chemical com-ponents were searched to establish the target data set. Cytoscape3.6.1 software was used to construct the complex network diagram of “active ingredient - target – disease”. The GO biological function enrichment analysis and KEGG pathway enrichment analysis were carried out through the annotation database of biological information (DAVID) to explore the mechanism of Gegen antidotes. Results: A total of 18 compounds were retrieved, 4 of which were active compounds; a total of 92 targets were retrieved. Through the evaluation of network topological characteristics, the screening of 8 potential targets was the most closely related to Gegen hangover. Using the DAVID database to analyze the potential target targets for gene GO function enrichment and KEGG pathway enrichment, 35 were screened. Biological processes and 28 signaling pathways are involved in the role of Pueraria hangover. The signaling pathways that are more closely related to Pueraria hangover include neuroactive ligand-receptor interaction, calcium signaling pathway, cholinergic synapse, adrenergic signal in cardiomyocytes, PI3K-AKT signaling pathway, VEGF signaling pathway, p53 signal pathways, signaling pathways such as NAFLD, and its main biological processes include estradiol response, synaptic transmission, cholinergic, adenylate cyclase inhibition of G protein- coupled acetylcholine receptor signaling pathway, and phospholipase C activation G protein- coupled acetylcholine receptor signaling pathway, γ-aminobutyric acid signaling pathway, positive regulation of RNA polymerase II promoter transcription, cytochrome c activation, and cysteine-type endopeptidase activity involved in apoptosis, thereby exerting the biological effects of multi-component, multi-target, multi-channel hangover. Conclusion: Network pharmacology provides research direction and scientific basis for the mechanism of Gegen hangover.