阿尔茨海默病嗅觉障碍中药用药规律的网络药理学研究

Study on network pharmacology of traditional Chinese medicine administration in olfactory disorders in Alzheimer's disease

目的利用网络药理学及数据挖掘方法初步探索中药调节阿尔茨海默病(AD)嗅觉障碍的物质基础及用药规律。方法通过OMIM、GeneCards、CTD等数据库分别获得AD和嗅觉障碍的相关靶点,取两者的交集靶点后,以在中药系统药理学数据库与分析平台(TCMSP)中类药性≥0.18且可匹配到相应的化合物为条件,进一步筛选获得AD嗅觉障碍的潜在作用靶点。应用TCMSP数据库收集潜在作用靶点的相关化合物、中药,在Cytoscape软件中构建靶点-化合物、靶点-化合物-中药网络,根据度值大小获得核心潜在作用靶点、核心候选化合物及核心候选中药。将获得的核心候选化合物及核心潜在作用靶点进行分子对接,初步验证预测结果。建立中药数据库,通过数据分析获得AD嗅觉障碍的中药用药规律。结果共获得AD及嗅觉障碍的疾病相关靶点2919、2358个,两者的交集靶点共946个;其中,符合类药性≥0.18且能匹配到相关化合物的靶点共245个,候选化合物1172个,候选中药406味。候选中药的药味以苦、辛、甘为主,药性主要为温,归经以肝、肺二经为要主。结论以网络药理学及数据挖掘的方法,较为系统的探索了中药调节AD嗅觉障碍的物质基础,获得了中药治疗AD嗅觉障碍的用药规律,为该病的治疗提供了理论依据及用药指导。

OBJECTIVE To explore the material basis and medication rule of traditional Chinese medicine regulating olfactory disorder in Alzheimer's disease.METHODS Firstly,the related targets of Alzheimer's disease and olfactory disorders were searched in OMIM,GeneCards,CTD and other databases.After the intersection targets of the two diseases were obtained,the potential targets of anosmia in Alzheimer's disease were further screened based on the drug-like properties≥0.18 in the TCMSP database.Secondly,TCMSP database was used to collect related compounds and traditional Chinese medicines of potential targets.Then,target-compound,target-compound and Chinese medicine network were constructed in Cytoscape software to calculate the degree value,and core potential targets,core candidate compounds and core candidate Chinese medicine were obtained according to the degree value.The core candidate compounds and core potential action targets obtained in the study were molecularly docked to verify the predicted results.Finally,the traditional Chinese medicine database was established,and the rule of using traditional Chinese medicine for olfactory disorders in Alzheimer's disease was obtained through data analysis.RESULTS A total of 2919 disease-related targets of Alzheimer's disease and 2358 disease-related targets of olfactory disorders were obtained,and a total of 946 intersecting targets of the two diseases were obtained.A total of 245 targets were consistent with drug-like properties≥0.18 and could be matched with related compounds.1172 candidate compounds and 406 candidate herbs were obtained.The taste of the candidate Chinese medicine is mainly bitter,sweet and pungent,and the drug property is mainly warm,and the two channels of liver and lung are the key.CONCLUSION Through network pharmacology and data mining,this study systematically explores the material basis for the regulation of olfactory disorders in Alzheimer's disease by traditional Chinese medicine,obtains the medication rules of traditional Chinese medicine for the treatment of olfactory disorders in Alzheimer's disease,and provides certain theoretical basis and medication guidance for the treatment of olfactory disorders in Alzheimer's disease.