应用整合药理学方法探讨半夏泻心汤治疗慢性萎缩性胃炎的作用机制

Mechanism ofBanxia Xiexin Decoction in treating chronic atrophic gastritis by integrated pharmacology

目的应用整合药理学方法探讨半夏泻心汤治疗慢性萎缩性胃炎(CAG)的作用机制。方法运用整合药理学平台(TCMIP)的中药数据库,得到治疗CAG临床效果确切的经典方剂半夏泻心汤的化学成分及对应药物靶标,通过Human Phenotype Ontology数据库得到CAG的疾病靶标并将其导入TCMIP,TCMIP基于蛋白质相互作用网络(PPI)数据库构建靶点相互作用网络,进而得到半夏泻心汤治疗CAG候选靶标,最后对候选靶标进行GO功能分析和KEGG通路富集分析,并结合文献研究得出半夏泻心汤治疗CAG可能的生物途径和过程。结果得到复方中存在的420个化学成分,预测出1 228个药物作用的预测靶点,并构建了中药靶点相互作用网络及相应的GO、KEGG富集分析结果;将得到的5个疾病靶标与中药预测的作用靶标结合,预测得到半夏泻心汤治疗CAG的候选靶标,并构建得到'半夏泻心汤所含中药-候选靶标分子网络'及'半夏泻心汤-候选靶标-CAG相关分子网络'。结论半夏泻心汤治疗CAG的作用机制可能与白介素、环氧化酶-2、MAPK级联激活、ERK蛋白磷酸化等生物学途径有关。

Objective Network pharmacology can show the characteristics of TCM compound prescriptions with multi-component,multi-target and overall synergistic action and provide a new strategy for the mechanism study of TCM compound prescriptions.Methods In this study,Banxia Xiexin Decoction,a classical prescription to treat chronic atrophic gastritis with definite clinical effect,was observed as a subject.First,the chemical constituents and corresponding drug targets of Banxia Xiexin Decoction were obtained by using the integrated pharmacological database of TCM(TCMIP).Then,chronic atrophic gastritis disease targets were obtained through Human Phenotype Ontology database.The target interaction network was constructed based on protein interaction network(PPI)database,and a candidate target of Banxia Xiexin Decoction for chronic atrophic gastritis was obtained.Finally,GO function analysis and KEGG pathway enrichment analysis of candidate targets were conducted,and the possible biological pathways and processes of Banxia Xiexin Decoction in the treatment of chronic atrophic gastritis were concluded through literature studies.Results Firstly,420 chemical constituents in the compound were obtained,1228 predictive targets of drug action were predicted,and the target interaction network of Chinese herbal medicine was constructed and the corresponding GO and KEGG enrichment analysis Results were obtained.Secondly,five disease targets were combined with the predictive targets of Chinese herbal medicine,and the candidate targets of Banxia Xiexin Decoction for chronic atrophic gastritis were predicted.The molecular networks of Chinese herbal medicine-candidate targets contained in Banxia Xiexin Decoction and related molecular networks of Banxia Xiexin Decoction-candidate targets-chronic atrophic gastritis were constructed.The Results showed that Banxia Xiexin Decoction played an important role in regulating the expression of autoimmune factors,reducing inflammation,nerve growth factor,regulating gastrointestinal motility,protecting gastric mucosa,energy metabolism,improving immunity,regulating cholinergic nerve and inhibiting the proliferation of tumor cells.Conclusion The results of network pharmacological analysis combined with the literature of Banxia Xiexin Decoction on chronic atrophic gastritis suggest that the mechanism of action of Banxia Xiexin Decoction may be related to some biological pathways,such as interleukin,cyclooxygenase-2,MAPK cascade and ERK phosphorylation.