基于网络药理学预测菟丝子对阿尔茨海默病的作用靶点及细胞信号通路研究

Predicting the Target and Pathway of Cuscuta on Alzheimer’s Disease Based on Network Pharmacology

目的使用网络药理学相关软件预测菟丝子有效成分在干预阿尔茨海默病(AD)的作用靶点及相关细胞信号通路。方法运用中药系统药理学数据库平台(TCMSP)获取菟丝子的有效成分及相关靶点,在基因数据库GeneCards平台获取AD的基因相关信息,用软件Cytoscape V3.2.1构建药物-成分-基因-疾病之间相互作用的网络并进行分析,并通过R×644.0.2软件及相关脚本运行疾病靶点与药物靶点,筛选出菟丝子治疗AD的潜在有效成分及主要作用靶点,在蛋白互作关系数据库(STRING)绘制蛋白质相互作用(PPI)网络图,最后运行R×644.0.2程序,生成基因本体(GO)功能和基因组百科全书(KEGG)富集分析图。结果预测得到菟丝子治疗AD的10个有效成分和90个潜在作用靶点,并通过通路富集分析推测菟丝子对AD的作用机制可能和PI3K-Akt信号通路、卡波西氏肉瘤相关疱疹病毒感染等通路等有关,发现CASP3、DECR1、MAPK8、ESR1、NOS3等靶点基因可能在干预AD中起到关键作用。结论通过网络药理学分析并推测了菟丝子可能通过多成分、多靶点的方式干预AD,其多与抑制APP过度裂解,Aβ过度堆积、Tau蛋白异常磷酸化、减少炎症因子的表达、降低相关疱疹病毒感染风险、调节雌激素等方面有关,为进一步研究AD的防治提供了理论依据。

Objective Use network pharmacology related software to predict the target of the effective components of Cuscuta in the intervention of Alzheimer’s disease and related cell signaling pathways.Methods The Chinese Medicine System Pharmacology Database Platform(TCMSP)was used to obtain the active ingredients and related targets of Cuscuta Seed.The gene-related information of Alzheimer’s disease was obtained from the GeneCards platform of the gene database.The software Cytoscape V3.2.1 was used to construct the drug-component-gene-The network of interactions between diseases is analyzed and the disease targets and drug targets are run through R×644.0.2 software and related scripts to screen out the potential effective ingredients and main targets of dodder in the treatment of Alzheimer’s disease,Then draw the PPI network diagram of the interaction between proteins in the protein interaction relation database(STRING),and finally run the R×644.0.2 program to generate the gene(GO)function enrichment analysis diagram and the metabolic pathway(KEGG)enrichment diagram.Results It is predicted that 10 active ingredients and 90 potential targets of dodder for Alzheimer’s disease are obtained,and through pathway enrichment analysis,it is speculated that the mechanism of dodder for Alzheimer’s disease may be related to the PI3K-Akt signaling pathway and Kaposi.Sarcoma-related herpes virus infection and other pathways,and found that CASP3,DECR1,MAPK8,ESR1,NOS3 and other target genes may play a key role in the intervention of Alzheimer’s disease.Conclusion Through network pharmacological analysis,it is speculated that Cuscuta may interfere with Alzheimer’s disease through a multi-component and multi-target approach,which is mostly related to inhibiting excessive cleavage of APP,excessive accumulation of Aβ,abnormal phosphorylation of Tau protein,and reducing the expression of inflammatory factors.The reduction of related herpes virus infections and the regulation of estrogen provide a theoretical basis for further research on the prevention and treatment of Alzheimer’s disease.