基于整合药理学的越鞠丸“异病同治”研究

Study on Yueju Wan for "different diseases with same treatment" based on integrative pharmacology

中药经典方剂越鞠丸具有理气解郁,宽中除满的功效,现用于抑郁症和胃肠道相关疾病的治疗。该文采用整合药理学的研究方法,对越鞠丸治疗抑郁症和胃肠道功能紊乱的作用靶标、信号通路进行预测,并探讨该方＂异病同治＂的分子机制。首先通过Human Phenotype Ontology数据库收集疾病靶标,得到抑郁症的疾病相关靶标共计201个,胃肠道功能紊乱相关靶标共计474个,两者共同靶标95个。其次用整合药理学平台进行药物靶标、GO功能、KEGG通路、核心靶标网络和中药-成分-关键药靶-通路网络的预测和分析,得到ATP1A1,KRAS,PRKAA1等关键靶标,并富集到神经元凋亡过程（neuron apoptotic process）、神经营养因子信号通路（neurotrophin signaling pathway）、5-羟色胺能突触（serotonergic synapse）、一氧化氮合酶活性调节（regulation of nitric-oxide synthase activity）以及胆汁分泌（bile secretion）、胃酸分泌（gastric acid secretion）等与抑郁症和胃肠道功能紊乱相关的功能和通路,最终推测5-羟色胺能突触、一氧化氮合酶活性的调节可能是抑郁症和胃肠道功能紊乱的共同过程。该文基于整合药理学分析方法整体认识越鞠丸的作用特点,有助于阐明其对于抑郁症和胃肠道功能紊乱异病同治的作用机制。

The traditional Chinese medicine prescription Yueju Wan has the function of regulating qi-flowing for activating stagnancy and resolving food stagnation,which is now used for the treatment of depression and gastrointestinal related diseases. In this study,an integrative pharmacological method was adopted to predict the targets and pathways of Yueju Wan and explore its molecular mechanism for depression and gastrointestinal dysfunction with the same treatment. First,disease targets were collected from Human Phenotype Ontology database,201 targets related to depression and 474 targets related to gastrointestinal dysfunction,including 95 common targets of these two. Then,the integrative pharmacology platform of traditional Chinese medicine（ TCMIP） was used to predict and analyze the drug targets,GO function,KEGG pathway,core targets network of Yueju Wan and heterogeneous network of TCM-chemical components-key drug targets-pathway. According to the integrative analysis,it is found that ATP1 A1,KRAS,and PRKAA1 were key targets,and neuron apoptotic process,neurotrophin signaling pathway,serotonergic synapse and regulation of nitric-oxide synthase activity were key pathways which played important roles in molecular mechanism of Yueju Wan for depression and gastrointestinal dysfunction.In conclusion,speculated serotonergic synapse and regulation of nitric-oxide synthase activity maybe the common process in depression and gastrointestinal dysfunction. This paper provided an overall understanding on Yueju Wan based on TCMIP,helping to elucidate the mechanism of the same treatment for different diseases,depression and gastrointestinal dysfunction.