Ji Shuangshuang, Long Sidan, Yang Yang, Liu Zihao, Wang Rui, Zhang Huifen, Zhang Shuxin
Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2022 Jul 18;2022:8211941. doi: 10.1155/2022/8211941. eCollection 2022.
Jiawei-Huang Lian-Gan Jiang decoction (JWHLGJD) was developed to treat and prevent the patients with colorectal adenomas (CRA) in China. This study is aimed to discover JWHLGJD's active compounds and demonstrate mechanisms of JWHLGJD against CRA through network pharmacology and molecular docking techniques.
All the components of JWHLGJD were retrieved from the pharmacology database of Traditional Chinese Medicine Systems Pharmacology (TCMSP). The GeneCards database, the Online Mendelian Inheritance in Man database (OMIM), the DrugBank database, and PharmGKB were used to obtain the genes matching the targets. Cytoscape created the compound-target network. The network of target protein-protein interactions (PPI) was constructed using the STRING database. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways involved in the targets were analyzed by using the DAVID database. Cytoscape created the component-target-pathway (C-T-P) network. AutoDock Vina software was used to verify the molecular docking of JWHLGJD components and key targets. Core genes linked with survival and tumor microenvironment were analyzed through the Kaplan-Meier plotter and TIMER 2.0 databases, respectively.
Compound-target network mainly contained 38 compounds and 130 targets of the JWHLGJD associated with CRA. TP53, MAPK1, JUN, HSP90AA1, and AKT1 were identified as core targets by the PPI network. KEGG pathway shows that the pathways in cancer, lipids, and atherosclerosis, PI3K-Akt signaling pathway and MAPK signaling pathway, are the most relevant pathways to CRA. The C-T-P network suggests that the active component in JWHLGJD is capable of regulating target genes of these related pathways. The results of molecular docking showed that berberine and stigmasterol were the top two compounds of JWHLGJD, which had high affinity with TP53 and MAPK1, respectively. And, MAPK1 exerted a more significant effect on the prognosis of adenocarcinoma, for it was highly associated with various immune cells.
Findings in this study provided light on JWHLGJD's active components, prospective targets, and molecular mechanism. It also gave a potential way to uncovering the scientific underpinning and therapeutic mechanism of traditional Chinese medicine (TCM) formulas.
加味黄连干姜汤（JWHLGJD）在中国用于治疗和预防大肠腺瘤（CRA）患者。本研究旨在通过网络药理学和分子对接技术发现JWHLGJD的活性成分，并阐明其抗CRA的作用机制。
从中药系统药理学（TCMSP）药理学数据库中检索JWHLGJD的所有成分。使用基因卡片数据库、人类孟德尔遗传在线数据库（OMIM）、药物银行数据库和药物基因组知识库（PharmGKB）获取与靶点匹配的基因。Cytoscape创建化合物-靶点网络。使用STRING数据库构建靶点蛋白-蛋白相互作用（PPI）网络。利用DAVID数据库分析参与靶点的基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路。Cytoscape创建成分-靶点-通路（C-T-P）网络。使用AutoDock Vina软件验证JWHLGJD成分与关键靶点的分子对接。分别通过Kaplan-Meier绘图仪和TIMER 2.0数据库分析与生存和肿瘤微环境相关的核心基因。
化合物-靶点网络主要包含38种化合物和130个与CRA相关的JWHLGJD靶点。PPI网络将TP53、MAPK1、JUN、HSP90AA1和AKT1鉴定为核心靶点。KEGG通路显示，癌症、脂质与动脉粥样硬化、PI3K-Akt信号通路和MAPK信号通路是与CRA最相关的通路。C-T-P网络表明JWHLGJD中的活性成分能够调节这些相关通路的靶基因。分子对接结果显示，小檗碱和豆甾醇分别是JWHLGJD中与TP53和MAPK1具有高亲和力的前两种化合物。并且，MAPK1对腺癌预后的影响更为显著，因为它与多种免疫细胞高度相关。
本研究结果揭示了JWHLGJD的活性成分、潜在靶点和分子机制。它还为揭示中药方剂的科学依据和治疗机制提供了一条潜在途径。
