β-细辛醚治疗帕金森病抑郁的网络药理学作用机制分析

Network Pharmacological Analysis on Mechanism of β-asarone in Treating Depression of Parkinson’s Disease

目的基于网络药理学分析β-细辛醚治疗帕金森病抑郁(DPD)的作用机制。方法利用TCMSP、Swiss Target Prediciton和PharmMapper数据库检索得到β-细辛醚的作用靶点,通过Genecard数据库和OMIM数据库检索DPD的疾病相关靶点,并通过UniProt数据库进行标准化。构建β-细辛醚和DPD的共有靶点韦恩图,对共有靶点进行蛋白互作(PPI)网络分析,以获取关键靶点信息;对共有靶点进行GO功能及KEGG通路富集分析;建立"药物-疾病-靶点-通路"网络,展示β-细辛醚治疗DPD过程中疾病-靶点-通路的关系。结果共得到β-细辛醚和DPD的共有靶点64个,包括ALB、c-FOS、EGFR、JUN、CASP3、PTGS2、IGF1、ESR1、APP等多个关键靶点。共有靶点涉及学习或记忆、突触后膜的内在成分、神经递质受体活性、突触后神经递质受体活动等与突触间神经递质及其受体密切相关的生物过程、分子功能及细胞组成,以及5-HT能神经突触、DA能神经突触和神经活性配体受体相互作用等信号通路。结论β-细辛醚可能通过对c-FOS、JUN、ALB、EGFR、CASP3、MAP2K1、MAPK14等靶点及相关通路的作用,进而影响5-HT能神经突触和DA能神经突触的损伤修复,发挥治疗DPD的作用。

Objective To analyze the target and mechanism of β-asarone in the treatment of depression in Parkinson’s disease(DPD) based on network pharmacology. Methods TCMSP, Swiss Target Prediction and PharmMapper databases were used to retrieve the targets of β-asarone. Genecard and OMIM databases were used to retrieve the DPD related targets,and Uniprot database was used to standardize the targets of β-asarone. The Venn diagram of common targets,PPI network and key targets’ information table of β-asarone and DPD were constructed.GO annotation and KEGG pathway enrichment analysis were carried out, and β-asarone-DPD-pathway-target network diagram was established to show the active characteristics of disease-target of β-asarone in the treatment of DPD. Results There were 64 common targets of β-asarone and DPD, including ALB, c-FOS, EGFR, JUN,CASP3, PTGS2, IGF1, ESR1, APP, and so on. These targets involve learning or memory, the intrinsic components of postsynaptic membrane, the activities of neurotransmitter receptors, the activities of postsynaptic neurotransmitter receptors, and other biological processes closely related to the intersynaptic interaction of neurotransmitters and their receptors,molecular functions and cell compositions,and signal pathways such as the interaction between serotonergic synapse, dopaminergic synapse and neuroactive ligand receptors. Conclusionβ-asarone may exert curative effects in the treatment of DPD through the c-FOS,JUN,ALB,EGFR,CASP3,MAP2 K1, MAPK14 and other proteins and related pathways, and then play a role in the repair of serotonergic synapse and dopaminergic synapse.