(1. College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029; 2. Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China)
摘要目的: 使用网络药理学和分子对接技术研究凉血消斑汤治疗寻常型银屑病的关键成分与靶标，并探讨其可能的作用机制。方法: 从中药系统药理学数据库（traditional Chinese medicine systems pharmacology, TCMSP）、中医药分子机制生物信息学数据库（bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, BATMAN-TCM）挖掘凉血消斑汤的有效成分并进行靶点预测。在GeneCards数据库中获取寻常型银屑病相关基因。通过Cytoscape 3.7.2软件构建凉血消斑汤成分靶点疾病网络，通过STRING和Metascape分析药物与疾病映射靶标蛋白质的相互作用，并进行富集分析，最后借助AutoDock Vina等软件将核心靶标蛋白与有效成分进行对接验证。结果： 凉血消斑汤治疗寻常型银屑病的关键靶点包括蛋白激酶1（AKT1）、血管内皮生长因子A（VEGFA）、白介素6（IL-6）、JUN蛋白（JUN）及前列腺素内过氧化物合酶2（PTGS2）等，关键的KEGG通路包括IL-17信号通路、PI3K-Akt信号通路及AGE-RAGE信号通路等，其中薯蓣皂苷元、山柰酚、木犀草素、黄芩素与PTGS2、AKT1等靶点的结合能较小。结论： 凉血消斑汤通过直接或间接调控IL-17及PI3K/AKT等信号通路，改善银屑病炎性浸润、角质形成细胞异常分化及异常新生血管生成等病理因素，从而发挥对银屑病的治疗作用。
Objective: To analyze the key components and targets of LiangxueXiaoban Decoction in the treatment of psoriasis vulgaris by network pharmacology and molecular docking, and to explore its possible mechanism. Methods: Traditional Chinese medicine systems pharmacology (TCMSP) and bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) were employed to search the effective active components and targets of LiangxueXiaoban Decoction. GeneCards database was employed to search the psoriasis vulgaris related genes. The drug-component-target-disease network and protein-protein interaction (PPI) network was constructed by STRING databaseand Cytoscape 3.7.2 software. Target gene functions and pathways were analyzed by bioinformatics annotation database(Metascape). Finally, Autodock software was applied in verifying the molecular docking between active ingredients and potential protein targets. Results: The key targets of LiangxueXiaoban Decoction in the treatment of psoriasis vulgaris are AKT1, VEGFA, IL-6, JUN and PTGS2, etc. The key KEGG pathways are IL-17 signaling pathway, PI3K-Akt signaling pathway and AGE-RAGE signaling pathway. The molecular docking results showed that diosgenin, kaempferol, luteolin, and baicalein can bind to targets such as PTGS2 and AKT1 with lower binding energy. Conclusion: LiangxueXiaoban Decoction can improve the pathological factors such as inflammatory infiltration of psoriasis, abnormal differentiation of keratinocytes and abnormal new angiogenesis by regulating IL-17 and PI3K/AKT signal pathways, which may contribute to its therapeutic role in psoriasis.
