远志治疗阿尔茨海默病的网络药理学作用机制

Network pharmacology mechanism study on the effective constituents of Polygala Tenuifolia for anti-Alzheimer's disease

目的:研究远志抗阿尔茨海默病的网络药理学机制。方法:通过阿尔茨海默病相关靶点、远志化学成分的收集,利用已建立的阿尔茨海默病多靶点预测平台及分子对接等方法,预测其中的有效成分及其作用靶点,构建了化学成分-靶点网络,靶点-靶点网络以及靶点-通路作用网络。结果:收集到化学成分100余个,其中36个成分可透过血脑屏障,预测结果发现,其主要作用靶点为ACh E,COX-2,TNF-α,Insulin-degrading enzyme和APP。化学成分-靶点网络分析结果表明,主要化学成分的结构类型有远志皂苷类、远志糖苷、远志灌木酮类、去甲哈尔满(β-咔唑啉)、远志口山酮、甾醇等,作用于ACh E,APP,M-TAU,GSK3β及5HT1A的维度较高。GO(gene-ontology)生物学通路及KEGG代谢通路富集分析结果显示,其化学成分主要作用通路为神经递质的释放、突触传导与突触可塑性、细胞凋亡调控、磷酸化途径、Ca离子信号传导途径等。结论:本研究从网络药理学角度初步分析得出远志是以多成分、多靶点、多通路的整合作用方式发挥抗阿尔茨海默病效应,为临床应用提供理论依据,同时也为远志多靶点多通路有效化学成分的进一步研究提供重要信息。

Objective： To clarify the network pharmacology mechanism of Polygala Tenuifolia against Alzheimer＇s disease. Methods： First,we collected the constituents of Polygala tenuifolia and key targets toward AD. Machine learning algorithms were applied to construct classifiers for predicting the effective constituents.Second,docking models were utilized for further evaluation. Finally, constituent-targetnetwork, target-target network and target-biology pathway network were built. Results： Through prediction of blood-brain penetration and validation,it was found that 36 chemical constituents could penetrate blood-brainbarrier among 100 collected compounds,thedominating targets of which involved ACh E,COX-2,TNF-α,Insulin-degrading enzyme and APP.Chemical constituent-target network confirmed that polygala saponins,glycosides of polygalaceae,chromeno [4,3-b] chromene-6,7-dione,norharman（ β-carbazoline）,polygalaxanthone III and sterol consisted of the main chemical constituent structures,which highly aimed at Ach E,APP,M-TAU,GSK3β and 5 HT1 A. GO（ gene-ontology） andKEGG enrichment analysis showed that the main pathways of these constituents involve neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis regulation,phosphorylation pathway,Ca2 ＋signaling pathway and so on. Conclusion： Polygala Tenuifolia could play a network mechanism of anti-Alzheimer＇s disease by integrating multi-constituent, multi-target and multi-pathway. This study may offer a deep insight for clinical application,moreover,it may contribute to the further research on this mechanism.