基于网络药理学研究豆腐果苷抗抑郁作用机制  

Study on antidepressant mechanism of helicid based on network pharmacology

作　　者：蒋臻熠 张远 李泽朋 张晓彤 张袁祥 童九翠[2] Jiang Zhenyi;Zhang Yuan;Li Zepeng;Zhang Xiaotong;Zhang Yuanxiang;Tong Jiucui(The Graduate School of Wannan Medical College,Wuhu 241002;Clinical Pharmacy Department of Yijishan Hospital of Wannan Medical College,Wuhu 241001)

机构地区：[1]皖南医学院研究生学院,芜湖241002 [2]皖南医学院弋矶山医院临床药学部,芜湖241001

出　　处：《安徽医科大学学报》2022年第12期1896-1901,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1808085MH290);安徽省教育厅自然重点项目(编号:KJ2021A0858);弋矶山医院引进人才科研基金(编号:YR202113);皖南医学院教学质量与教学改革工程项目(编号:2020kcbz12)。

摘　　要：目的基于网络药理学和分子对接技术筛选豆腐果苷干预抑郁症的作用靶点,研究豆腐果苷对慢性不可预知温和应激(CUMS)大鼠海马、前额叶皮质、纹状体及缰核中相关靶点表达水平的影响。方法通过SwissTargetPrediction数据库预测豆腐果苷的作用靶点,利用GeneCards、DisGeNet、TTD、DRUGBANK数据库筛选抑郁症相关靶点,取两者交集靶点;使用Metascape平台进行基因富集分析,并构建“豆腐果苷-抑郁症-通路”网络;采用AutoDock vina进行分子对接研究;qRT-PCR检测豆腐果苷对大鼠各组织中5-羟色胺1A受体(HTR1A)、腺苷A1受体(ADORA1)、腺苷A2A受体(ADORA2A)mRNA表达水平的影响。结果获得豆腐果苷靶点81个,抑郁症靶点1640个,两者交集靶点共40个;交集靶点主要被富集于环磷酸腺苷(cAMP)、磷脂酰肌醇-3-羟激酶(PI3K)-蛋白激酶B(Akt)、丝裂原活化蛋白激酶(MAPK)等信号通路;分子对接结果显示豆腐果苷与大部分靶点的结合活性较好;豆腐果苷上调CUMS大鼠海马、前额叶皮质、纹状体及缰核中HTR1A、ADORA1、ADORA2A mRNA的表达水平。结论豆腐果苷可能通过HTR1A、ADORA1、ADORA2A等靶点,作用于cAMP、PI3K-Akt、MAPK等信号通路干预抑郁症。Objective To screen the target of helicid in the intervention of depression based on network pharmacology and molecular docking,and to study the effect of helicid on the expression level of related targets in hippocampus,prefrontal cortex,striatum and habenular nucleus of chronic unpredictable mild stress(CUMS)rats.Methods The target of helicid was predicted by SwissTargetPrediction database,and the depression related targets were screened by GeneCards、DisGeNet、TTD and DRUGBANK databases;the metascape platform was used for gene enrichment analysis,and the"helicid-depression-pathway"network was constructed;Autodock Vina was used for molecular docking research;qRT-PCR was used to detect the effect of helicid on the mRNA expression of HTR1A,ADORA1 and ADORA2A in rat tissues.Results The 81 helicid targets and 1640 depression targets were obtained,including 40 intersecting targets;the key targets were mainly enriched in cAMP signal pathway,PI3K-Akt signal pathway,MAPK signal pathway and so on;the results of molecular docking showed that the binding activity of helicid with most targets was good;helicid up-regulated the expression levels of HTR1A,ADORA1 and ADORA2A mRNA in hippocampus,prefrontal cortex,striatum and habenular nucleus of CUMS rats.Conclusion Helicid may act on cAMP,PI3K-Akt,MAPK and other signal pathways to intervene depression through HTR1A,ADORA1 and ADORA2A.

关 键 词：豆腐果苷 抑郁症 网络药理学 药物靶点 

分 类 号：R285.5[医药卫生—中药学]