基于网络药理学探索石菖蒲-川芎配伍治疗阿尔兹海默病的作用机制研究

Study on the Mechanism of the Combination of Shichangpu and Chuanxiong in Treating AD Based on Network Pharmacology

目的运用网络药理学软件预测石菖蒲-川芎配伍治疗阿尔兹海默病(Alzheimer’s Disease,AD)的作用靶点,构建成分疾病靶点网络并分析其作用信号通路,从系统水平深入探讨其抗AD的作用分子机制。方法运用中药成分数据库(TCMID)与中药系统药理学数据库(TCMSP)收集石菖蒲和川芎的潜在活性成分。通过治疗靶点数据库(TTD)和药物数据库(Drugbank)检索获得AD作用靶点,并运用小分子活性数据库(PubChem)和靶点预测数据库(Swiss Target Prediction)根据石菖蒲、川芎潜在活性成分二维或三维结构相似性预测出相关作用靶点,将药物靶点与疾病靶点重叠部分筛选得出药物与疾病共同作用靶点,利用Cytoscape 3.2.1软件建立药物成分-疾病靶点PPI网络;运用基因分析软件(DAVID)对靶点进行基因功能的基因本体论(GO)分析和代谢途径分析数据库(KEGG)进行通路富集分析阐明石菖蒲-川芎配伍与AD的关系。结果石菖蒲-川芎配伍活性成分与AD疾病靶点网络包括10个化合物和51个靶点,参与相关代谢通路28条,包括神经配体-受体相互作用、Rap1信号通路、AD信号通路、Ca2+信号通路、PI3K-AKT信号转导通路等。结论石菖蒲-川芎是以多个靶点、多途径相互作用发挥治疗AD的药理作用,其多与增加突触间信息传递、促进神经突触的生长及突触可塑性、降低Aβ的生成与抑制Tau蛋白的过度磷酸化、抵抗抑制性神经递质释放以及增强胆碱能系统功能密切相关。

Objective To Use network pharmacology software to predict the therapeutic targets of Acorus tatarinawii Schott-Ligusticum chuanxiong Hort compatibility on Alzheimer′s disease(AD),construct the constituent disease target network and analyze its signaling pathways,and further explore the molecular mechanism of its anti-AD effect at the system level.Methods The potential active ingredients of Acorus tatarinawii Schott-Ligusticum chuanxiong Hort were collected by TCMID database and TCMSP pharmacological analysis platform.The target of AD was retrieved from TTD database and Drugbank database,and the target of AD was predicted based on the two-dimensional or three-dimensional structural similarity of potential active components of Acorus tatarinawii Schott-Ligusticum chuanxiong Hort by using PubChem and Swans Target Prediction database.The overlapping parts of drug target and disease target were screened to obtain the target of drug-disease interaction.Cytoscape3.2.1 software was used to identify the target of drug-disease interaction.The PPI network of drug component-disease target was established and the relationship between compatibility of Acorus tatarinawii Schott-Ligusticum chuanxiong Hort and AD was clarified by GO analysis of gene function and KEGG pathway enrichment analysis by DAVID gene enrichment analysis software.Results The active components of Acorus tatarinawii Schott-Ligusticum chuanxiong Hort compatibility and AD disease target network consisted of 10 compounds and 51 targets.They participated in 28 related metabolic pathways,including neuroligand-receptor interaction,Rap1 signaling pathway,Alzheimer′s disease signaling pathway,Ca2+signaling pathway,PI3K-AKT signaling pathway and so on.Conclusion Acorus tatarinawii Schott-Ligusticum chuanxiong Hort plays a pharmacological role in the treatment of AD through multi-target and multi-pathway interaction,which is closely related to increasing the information transmission between synapses,promoting the growth of synapses and synaptic plasticity,reducing the production of Abeta and inhibiting the over-phosphorylation of tau protein,resisting the release of inhibitory neurotransmitters and enhancing the function of cholinergic system.