淫羊藿治疗阿尔茨海默病作用机制的网络药理学与分子对接研究

Network Pharmacological Analysis and Molecular Docking of Epimedium in the Treatment of Alzheimer’s Disease

目的基于网络药理学与分子对接的方法探讨淫羊藿治疗阿尔茨海默病(AD)的潜在作用机制。方法通过中医药系统药理学数据库和分析平台(TCMSP)检索和筛选淫羊藿的相关成分和作用靶点,从GeneCards数据库获取AD相关靶点,取两者共同靶点,运用Cytoscape 3.82对共同靶点进行拓扑学分析得到核心靶点,利用DAVID数据库、RStudio软件对核心靶点基因进行GO和KEGG富集分析,对主要成分和靶点进行分子对接验证。结果①从TCMSP数据库检索出淫羊藿中有130种活性成分和1620个靶点,并从中筛选出11种有效成分、149个靶点。从GeneCards数据库检索AD有11032种靶点,其中淫羊藿有效成分靶点与AD共同靶点有62种,根据拓扑分析筛选出核心靶点20种。②生物过程主要涉及化学性突触传递、药物反应、信号转导、细胞增殖的负调控、细胞增殖的正调控、G蛋白偶联受体信号通路、腺苷酸环化酶激活肾上腺素能受体信号通路、ERK1和ERK2级联的正调节、平滑肌收缩的调节等方面;分子功能主要涉及蛋白质结合、蛋白质同源二聚化活性、药物结合、血清素结合、肾上腺素结合、神经递质受体活性、G蛋白偶联5-羟色胺受体活性、蛋白质异二聚活性、α2肾上腺素能受体活性等方面;细胞组成主要涉及质膜、突触后膜、神经元细胞体、神经元投射等方面;③主要代谢通路包括神经活性配体-受体相互作用通路、钙信号通路、5-羟色胺能突触通路、缝隙连接通路、cGMP-PKG信号通路、cAMP信号通路、雌激素信号通路、胆碱能突触通路、PI3K-Akt信号通路等。④2,7-二氢高刺桐春、去水淫羊藿分别与ACHE、SLC6A4稳定地结合。结论淫羊藿通过多靶点、多通路治疗AD,为以后科研以及临床研究提供理论依据。

Objective to explore the potential mechanism of Epimedium in the treatment of Alzheimer’s disease(AD)based on the method of network pharmacology and molecular docking.Methods The components and targets of Epimedium were searched and screened through the Traditional Chinese Medicine Systems Pharmacology(TCMSP).Targets associated with AD were obtained from GeneCards database.The intersection of targets of Epimedium and AD was used to obtain the common target of both,and Cytoscape3.82 was used to conduct topological analysis of the common target to obtain the core target.GO analysis and KEGG analysis were performed on the core target genes using DAVID database and RStudio software.Finally,it dentified components and targets by molecular docking.Results There were 130 components and 1620 targets in Epimedium,and 11 active components and 149 targets were selected from THE TCMSP database.In AD,11032 targets were selected from GeneCards database,among which 62 common targets of active components and AD were identified,and 20 core targets were selected from topological analysis.GO analysis:The biological process mainly involved Chemical synaptic transmission,Response to drug,Signal transduction,Negative regulation of cell proliferation,Positive regulation of cell proliferation,G-protein coupled receptor signaling pathway,Adenylate cyclase activation adrenergic receptors signaling pathways,Positive regulation of ERK1 and ERK2 cascade,The regulation of smooth muscle contraction,etc;Molecular functions mainly involved Protein binding,Protein homologous dimerization activity,Drug binding,Serotonin binding,Epinephrine binding,Neurotransmitter receptor activity,G-protein coupled serotonin receptor activity,Protein heterodimerization activity,Alpha2-adrenergic receptor activity and so on.Cellular components mainly involved Plasma membrane,Postsynaptic membrane,Neuron cell body and Neuron projection,etc.KEGG analysis:The major metabolic pathway mainly involved the Neuroactive ligand-receptor interaction pathways,the Calcium signaling pathways,the Serotonergic synaptic pathways,the Gap junction pathways,the cGMP-PKG signaling pathways,the cAMP signaling pathways,the Estrogen Signal pathway,the cholinergic synaptic pathway,the PI3K-Akt signaling pathway,etc.Molecular docking:2,7-Dihydrohomoerysotrine and Anhydroicaritin respectively bonded with ACHE and SLC6A4.Conclusion Epimedium can treat AD through multiple targets and multiple pathways,which provides theoretical basis for future scientific research and clinical research.