Zhang Wen, Tang Shi-Huan, Zhang Yi, Li De-Feng, Yang Hong-Jun, Zhang Yi, Guo Fei-Fei
College of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2018 Apr;43(7):1352-1359. doi: 10.19540/j.cnki.cjcmm.20180123.001.
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 ATP1A1, 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.
中药方剂越鞠丸具有行气解郁、消食化积的功效，目前用于治疗抑郁症和胃肠道相关疾病。在本研究中，采用整合药理学方法预测越鞠丸的靶点和通路，并探索其对抑郁症和胃肠道功能障碍同治的分子机制。首先，从人类表型本体数据库收集疾病靶点（201个与抑郁症相关的靶点和474个与胃肠道功能障碍相关的靶点，其中这两者有95个共同靶点）。然后，利用中药整合药理学平台（TCMIP）预测和分析越鞠丸的药物靶点、GO功能、KEGG通路、核心靶点网络以及中药-化学成分-关键药物靶点-通路的异质网络。通过整合分析发现，ATP1A1、KRAS和PRKAA1是关键靶点，神经元凋亡过程、神经营养因子信号通路、5-羟色胺能突触和一氧化氮合酶活性调节是关键通路，它们在越鞠丸治疗抑郁症和胃肠道功能障碍的分子机制中发挥重要作用。总之，推测5-羟色胺能突触和一氧化氮合酶活性调节可能是抑郁症和胃肠道功能障碍的共同过程。本文基于TCMIP对越鞠丸进行了全面的解读，有助于阐明抑郁症和胃肠道功能障碍这两种不同疾病同治的机制。
