Zheng Lie, Wen Xin-Li, Dai Yan-Cheng
Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an 730000, Shaanxi Province, China.
Department of Gastroenterology, Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China.
World J Clin Cases. 2021 Sep 16;9(26):7653-7670. doi: 10.12998/wjcc.v9.i26.7653.
Ulcerative colitis (UC) is a refractory intestinal disease with alternating onset and remission and a long disease course, which seriously affects the health and quality of life of patients. The goal of treatment is to control clinical symptoms, induce and maintain remission, promote mucosal healing, and reduce recurrence. Clinical trials have shown unsatisfactory clinical response rates. As a supplementary alternative medicine, traditional Chinese medicine has a rich history and has shown good results in the treatment of UC. Because of the quality of herbal medicine and other factors, the curative effect of traditional Chinese medicine is not stable enough. The mechanism underlying the effect of Jianpi Qingchang Huashi Recipe (JPQCHSR) on inducing UC mucosal healing is not clear.
To investigate the potential mechanism of JPQCHSR for the treatment of UC based on network pharmacology and molecular docking.
Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to extract the active components and action targets of JPQCHSR, and the target names were standardized and corrected through UniProt database. The related targets of UC were obtained through GeneCards database, and the intersection targets of drugs and diseases were screened by jvenn online analysis tool. The visual regulatory network of "Traditional Chinese medicine-active components-target-disease" was constructed using Cytoscape software, the protein interaction network was constructed using STRING database, and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways was conducted through R software. At last, the active components were docked with the core target through SYBYL-X 2.1.1 software.
Through database analysis, a total of 181 active components, 302 targets and 205 therapeutic targets were obtained for JPQCHSR. The key compounds include quercetin, luteolin, kaempferol, The core targets involved STAT3, AKT1, TP53, MAPK1, MAPK3, JUN, TNF, A total of 2861 items were obtained by GO enrichment analysis, and 171 items were obtained by KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. The results of molecular docking showed that the key active components in JPQCHSR had certain affinity with the core target.
The treatment of UC with JPQCHSR is a complex process of multi-component, multi-target and multi-pathway regulation. The mechanism of this Recipe in the treatment of UC can be predicted through network pharmacology and molecular docking, so as to provide theoretical reference for it to better play its therapeutic role.
溃疡性结肠炎（UC）是一种起病与缓解交替、病程较长的难治性肠道疾病，严重影响患者的健康和生活质量。治疗目标是控制临床症状、诱导并维持缓解、促进黏膜愈合及减少复发。临床试验显示临床有效率不尽人意。作为补充替代医学，中医药历史悠久，在UC治疗中已显示出良好效果。但受中药质量等因素影响，中医药疗效不够稳定。健脾清肠化湿方（JPQCHSR）诱导UC黏膜愈合的作用机制尚不明确。
基于网络药理学和分子对接研究JPQCHSR治疗UC的潜在机制。
运用中药系统药理学数据库与分析平台提取JPQCHSR的活性成分及作用靶点，通过UniProt数据库对靶点名称进行标准化及校正。通过GeneCards数据库获取UC相关靶点，运用jvenn在线分析工具筛选药物与疾病的交集靶点。利用Cytoscape软件构建“中药-活性成分-靶点-疾病”可视化调控网络，运用STRING数据库构建蛋白质相互作用网络，通过R软件进行基因本体论和京都基因与基因组百科全书通路富集分析。最后，通过SYBYL-X 2.1.1软件将活性成分与核心靶点进行对接。
通过数据库分析，共获得JPQCHSR的181个活性成分、302个靶点及205个治疗靶点。关键化合物包括槲皮素、木犀草素、山奈酚等。核心靶点涉及信号转导和转录激活因子3（STAT3）、蛋白激酶B（AKT1）、肿瘤蛋白p53（TP53）、丝裂原活化蛋白激酶1（MAPK1）、丝裂原活化蛋白激酶3（MAPK3）、原癌基因蛋白c-Jun（JUN）、肿瘤坏死因子（TNF）等。基因本体论富集分析共获得2861项，京都基因与基因组百科全书通路富集分析获得171项。分子对接结果显示，JPQCHSR中的关键活性成分与核心靶点具有一定亲和力。
JPQCHSR治疗UC是一个多成分、多靶点、多途径调控的复杂过程。可通过网络药理学和分子对接预测该方治疗UC的机制，为其更好发挥治疗作用提供理论参考。
