基于生物信息学、网络药理学与分子对接研究八桂天龙散治疗阿尔茨海默病的机制

Mechanisms of Bagui Tianlong Powder(八桂天龙散)Treating Alzheimer’s Disease Based on Bioinformatics,Network Pharmacology and Molecular Docking

目的基于生物信息学、网络药理学与分子对接探讨八桂天龙散治疗阿尔茨海默病(alzheimer’s disease,AD)的作用靶点与分子机制。方法从TCMSP、HIT、HERB数据库检索八桂天龙散活性成分,通过Swiss Target Prediction平台预测潜在作用靶点。采用GEO2R分析AD的差异基因,应用GeneCards、OMIM、DisGeNET数据库筛选AD靶点,交集获得八桂天龙散治疗AD的可能潜在作用靶点。采用STRING平台构建PPI网络,Cytoscape软件网络拓扑计算筛选潜在关键靶点,R语言进行GO及KEGG通路富集分析,构建“中药-活性成分-靶点-信号通路-疾病”网络。分子对接预测潜在活性成分和靶点的结合性能。结果筛选八桂天龙散有效活性成分115种,相应基因靶点1666个。AD差异基因2725个,靶点2236个。八桂天龙散治疗AD的潜在靶点99个,其中关键靶点为MAPK1、FN1、EGFR。KEGG富集分析显示关键信号通路包括PI3K-Akt、MAPK、Rap1、Ras、HIF-1、LTP等信号通路。分子对接结果显示人参二醇、次甲丹参醌可能是八桂天龙散治疗AD的核心活性化合物。结论八桂天龙散通过多组分、多靶点、多通路协同机制干预AD,与氧化应激、神经炎症、谷氨酸能突触、长时程增强、自噬、凋亡等机制密切相关。

Objective This study aimed to explore the therapeutic target and molecular mechanism of Bagui Tianlong Powder(八桂天龙散)treating alzheimer's disease(AD)based on bioinformatics,network pharmacology and molecular docking.Meth⁃ods We retrieved the active ingredients of Bagui Tianlong Powder using traditional Chinese medicine systems pharmacology data⁃base and analysis platform(TCMSP),Herbal Ingredients'Targets Platform(HIT)and HERB databases and predicted potential targets using the Swiss Target Prediction platform.The differential genes of AD were analyzed by GEO2R,and AD targets were screened by GeneCards,OMIM and DisGeNET databases.After the intersection of GEO2R with GeneCards,OMIM and DisGeN⁃ET databases,the possible potential targets of Bagui Tianlong Powder in the treatment of AD were obtained.We used STRING platform to build PPI network,screened the potential key targets through network topology calculation using Cytoscape software,and performed GO and KEGG enrichment analyses using R software.Following that,the“herbs-active ingredients-targets-signaling pathways-diseases”network was created.Finally,the binding properties of potential active ingredients and targets were predicted by molecular docking.Results A total of 115 active ingredients of Bagui Tianlong Powder and 1666 corresponding gene targets were screened.Meanwhile,2725 differential genes and 2236 targets in AD were screened.There were 99 potential targets of Bagui Tianlong Powder in the treatment of AD,among which the key targets were MAPK1,FN1 and EGFR.The KEGG path⁃way enrichment analysis result was mainly associated with the PI3K-Akt signaling pathway,MAPK signaling pathway,Rap1 sig⁃naling pathway,Ras signaling pathway,HIF-1 signaling pathway and LTP signaling pathway.Molecular docking results con⁃firmed the crucial active ingredients of Bagui Tianlong Powder in the treatment of AD might be panaxadiol and methylenetanshin⁃quinone.Conclusion This study reveals that Bagui Tianlong Powder may act on AD through the synergy mechanism of multi-component,multi-target and multi-channel.This may be closely related to oxidative stress,neuroinflammation,glutamatergic synapse,long-term potentiation,autophagy,apoptosis and other mechanisms.