基于网络药理学和分子对接探讨白屈菜生物碱治疗功能性腹痛的作用机制

Study on Mechanism of Baiqucai(Chelidonium majus)in Treatment of Functional Abdominal Pain Based on Network Pharmacology and Molecular Docking Technology

目的结合网络药理学和分子对接技术研究白屈菜生物碱治疗功能性腹痛的作用机制。方法收集通过高效液相色谱与四级杆飞行时间质谱联用技术(HPLC-Q-TOF/MS)鉴定出的白屈菜生物碱,通过SwissTargetPrediction预测其作用的靶点;从GeneCards、Drugbank、OMIM和TTD数据库获取功能性腹痛(FAP)的相关靶点。取两者靶点的交集作为白屈菜生物碱和抗FAP相关的作用靶点。通过STRING构建蛋白互作网络并进行拓扑分析得到白屈菜碱抗FAP的核心靶点。使用Metascape进行GO生物功能和KEGG通路富集分析;通过SwissDock将代表性白屈菜碱(木兰花碱)与核心靶点进行分子对接。结果白屈菜碱抗FAP靶点共有134个,关键靶点10个;GO、KEGG富集分别得到取排名前20个条目,主要涉及癌症通路、癌症中的蛋白聚糖、钙信号通路、5-羟色胺能突触、cAMP信号通路和轴突引导通路等;分子对接结果显示,木兰花碱与核心靶点都表现出较强的结合能力。结论白屈菜主要通过SRC、AKT1、EGFR、CASP3、MAPK3等多靶点干预的网络模式产生中枢镇痛作用,从而发挥抗FAP活性。

Objective To study the mechanism of Baiqucai(Chelidonium majus)alkaloids in the treatment of functional abdominal pain by combining network pharmacology and molecular docking technology.Methods Alkaloids identified by HPLC-Q-TOF/MS technology were collected,and their targets were predicted by SwissTargetPrediction and the related targets of functional abdominal pain(FAP)were obtained from GeneCards,Drugbank,OMIM and TTD databases.The intersection of the two targets was taken as anti-FAP targets of alkaloids.The protein interaction network was constructed by STRING and topological analysis was performed to obtain the core targets.GO biofunction and KEGG pathway enrichment analysis using Metascape.The molecular docking of representative Baiqucai(Chelidonium majus)(magnolanine)to core targets were jointed by SwissDock.Results There were 134 anti-FAP targets of Baiqucai(Chelidonium majus)alkaloids,and 10 key targets.GO and KEGG enrichment obtained the top 20 items,mainly involving pathways in cancer,proteoglycans in cancer,calcium signaling pathway,serotonergic synapse,cAMP signaling pathway and axon guidance pathways,etc.The results of molecular docking showed that magnolanine showed strong binding ability to core targets.Conclusion Baiqucai(Chelidonium majus)mainly produces central analgesic effect through the network mode of SRC,AKT1,EGFR,CASP3,MAPK3 and other multi-target interventions,thereby exerting anti-FAP activity.