Zheng Lie, Ji Yong-Yi, Dai Yan-Cheng, Wen Xin-Li, Wu Shi-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 Neurology, Xi'an Hospital of Traditional Chinese Medicine, Xi'an 710021, Shaanxi Province, China.
World J Clin Cases. 2022 Aug 6;10(22):7674-7685. doi: 10.12998/wjcc.v10.i22.7674.
Inflammatory bowel disease (IBD) is a complex chronic IBD that is closely associated with risk factors such as environment, diet, medications and lifestyle that may influence the host microbiome or immune response to antigens. At present, with the increasing incidence of IBD worldwide, it is of great significance to further study the pathogenesis of IBD and seek new therapeutic targets. Traditional Chinese medicine (TCM) treatment of diseases is characterized by multiple approaches and multiple targets and has a long history of clinical application in China. The mechanism underlying the effect of zedoary turmeric-trisomes on inducing mucosal healing in IBD is not clear.
To explore the effective components and potential mechanism of zedoary turmeric-trisomes in the treatment of IBD with intestinal fibrosis using network pharmacology and molecular docking techniques.
The chemical constituents and targets of and were screened using the TCMSP database. The GeneCards database was searched to identify targets associated with intestinal fibrosis in IBD. The intersection of chemical component targets and disease targets was obtained using the Venny 2.1 online analysis platform, and the common targets were imported into the STRING 11.0 database to construct a protein interaction regulatory network. A "zedoary turmeric-trisomes-chemical composition-target-disease" network diagram was subsequently constructed using Cytoscape 3.7.2 software, and the topological properties of the network were analyzed using the "Network Analysis" plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the common targets were performed using the DAVID 6.8 database to elucidate the mechanism of zedoary turmeric-trisomes in the treatment of IBD. Subsequently, molecular docking of the compounds and targets with the highest intermediate values in the "zedoary turmeric-trisomes-chemical composition-target-disease" network was performed using Sybyl-x 2.1.1 software.
A total of 5 chemical components with 60 targets were identified, as well as 3153 targets related to IBD and 44 common targets. The protein-protein interaction network showed that the core therapeutic targets included JUN, MAPK14, CASP3, AR, and PTGS2. The GO enrichment analysis identified 759 items, and the KEGG enrichment analysis yielded 52 items, including the cancer pathway, neuroactive ligand-receptor interaction, hepatitis B, and the calcium signaling pathway, reflecting the complex biological processes of the multicomponent, multitarget and multipathway treatment of diseases with zedoary turmeric-trisomes. Molecular docking showed that the compound bonded with the target through hydrogen bond interactions and exhibited good docking activity.
This study identified the potential mechanism of action of zedoary turmeric-trisomes in the treatment of inflammatory bowel fibrosis using network pharmacology and molecular docking technology, providing a scientific basis for further expansion of their clinical use.
炎症性肠病（IBD）是一种复杂的慢性疾病，与环境、饮食、药物和生活方式等风险因素密切相关，这些因素可能影响宿主微生物群或对抗原的免疫反应。目前，随着全球IBD发病率的不断上升，进一步研究IBD的发病机制并寻找新的治疗靶点具有重要意义。中医治疗疾病具有多途径、多靶点的特点，在中国有着悠久的临床应用历史。莪术油三醇诱导IBD黏膜愈合的作用机制尚不清楚。
运用网络药理学和分子对接技术，探讨莪术油三醇治疗IBD伴肠纤维化的有效成分及潜在机制。
利用中药系统药理学数据库与分析平台（TCMSP）筛选莪术油三醇的化学成分及靶点。通过搜索基因卡片（GeneCards）数据库，识别与IBD肠纤维化相关的靶点。使用Venny 2.1在线分析平台获取化学成分靶点与疾病靶点的交集，并将共同靶点导入STRING 11.0数据库构建蛋白质相互作用调控网络。随后，使用Cytoscape 3.7.2软件构建“莪术油三醇-化学成分-靶点-疾病”网络图，并使用“网络分析”插件分析网络的拓扑性质。利用DAVID 6.8数据库对共同靶点进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，以阐明莪术油三醇治疗IBD的机制。随后，使用Sybyl-x 2.1.1软件对“莪术油三醇-化学成分-靶点-疾病”网络中中间值最高的化合物与靶点进行分子对接。
共鉴定出5种化学成分，60个靶点，以及3153个与IBD相关的靶点和44个共同靶点。蛋白质-蛋白质相互作用网络显示，核心治疗靶点包括JUN、MAPK14、CASP3、AR和PTGS2。GO富集分析确定了759个条目，KEGG富集分析产生了52个条目，包括癌症通路、神经活性配体-受体相互作用、乙型肝炎和钙信号通路，反映了莪术油三醇多成分、多靶点、多途径治疗疾病的复杂生物学过程。分子对接显示，化合物通过氢键相互作用与靶点结合，具有良好的对接活性。
本研究运用网络药理学和分子对接技术，明确了莪术油三醇治疗炎症性肠纤维化的潜在作用机制，为进一步扩大其临床应用提供了科学依据。
