Zhang Xiao-Wen, Liu Ai-Min, Zhao Jing-Jing, Guo Jia, Chen Xin-Yi, Qu Xiao-Xiao
Henan University of Chinese Medicine Zhengzhou 450046,China.
Henan Provincial Hospital of Traditional Chinese Medicine Zhengzhou 450002,China.
Zhongguo Zhong Yao Za Zhi. 2021 Feb;46(4):894-901. doi: 10.19540/j.cnki.cjcmm.20201117.401.
To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.
通过网络药理学和分子对接研究麻黄连翘赤小豆汤治疗湿疹的分子机制。首先，利用中药系统药理学数据库与分析平台（TCMSP）挖掘麻黄连翘赤小豆汤中各药物的活性成分并预测其靶点，利用通用蛋白质数据库（Uniprot）规范靶点蛋白名称，通过基因卡片数据库（GeneCards）、在线孟德尔遗传性人类疾病数据库（OMIM）、药物基因组学知识库（PharmGkb）、药物银行数据库（DrugBank）等数据库获取湿疹的疾病靶点。接着，筛选出药物靶点与疾病靶点共同作用的潜在靶点绘制韦恩图，使用Cytoscape 3.6.1软件筛选并构建“活性成分-核心靶点”网络。利用STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络，使用R语言进行基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析。最后，通过AutoDock软件对药物的主要活性成分与核心靶点进行分子对接验证。研究表明，筛选出麻黄连翘赤小豆汤治疗湿疹的74个活性成分和103个靶点。主要活性成分包括槲皮素、木犀草素、汉黄芩素、山奈酚，主要靶点包括环氧化酶-1（PTGS1）、雌激素受体1（ESR1）、过氧化物酶体增殖物激活受体γ（PPARG）、丝裂原活化蛋白激酶3（MAPK3）。此外，通过PPI网络计算得出8个关键靶点，包括丝裂原活化蛋白激酶8（MAPK8）、丝裂原活化蛋白激酶3（MAPK3）、原癌基因蛋白c-Jun（JUN）、丝裂原活化蛋白激酶14（MAPK14）、肿瘤蛋白p53（TP53）、丝裂原活化蛋白激酶1（MAPK1）、雌激素受体1（ESR1）和核因子κB亚基p65（RELA）。GO富集分析涉及2024个生物学过程、81个细胞成分和140个分子功能。进行KEGG通路富集分析筛选出158条与湿疹相关的通路，主要作用于晚期糖基化终末产物受体（AGE-RAGE）信号通路、白细胞介素-17（IL-17）信号通路、病毒相关通路，分子对接结果表明主要活性化合物能分别与代表性靶点结合并表现出良好亲和力。研究证明麻黄连翘赤小豆汤治疗湿疹涉及多条信号通路和生物学过程，主要活性成分（如槲皮素、木犀草素、汉黄芩素、山奈酚）与关键靶点（如MAPK8、MAPK3、JUN、MAPK14、TP53、MAPK1、ESR1、RELA）的结合可能是重要作用机制之一。
