龙胆泻肝汤治疗特应性皮炎可能的分子机制及生物学过程

The possible molecular mechanism and biological process of treating atopic dermatitis with the Longdan Xiegan decoction

目的:利用网络药理学探索龙胆泻肝汤治疗特应性皮炎的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)和BATMAN-TCM数据库挖掘龙胆泻肝汤的有效成分和作用靶点,利用CTD数据库筛选疾病靶点。将药物与疾病的交集靶点构建蛋白质-蛋白质相互作用网络,运用Cytoscape 3.7.2构建“疾病-药物-靶点-基因”四维网络,借助DAVID数据库对靶点进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,最终使用Auto Dock进行分子对接验证。结果:从龙胆泻肝汤中筛选出有效成分195个、作用靶点328个,其中与特应性皮炎疾病密切相关的靶点79个。经筛选,GO功能富集分析得到条目295个,KEGG通路富集分析得到信号通路86条。分子对接结果显示复方活性成分与核心靶点结合程度较好。结论:龙胆泻肝汤治疗特应性皮炎主要通过槲皮素、山柰酚、豆甾醇等活性化合物作用于白细胞介素-6(Interleukin-6,IL-6)、前列素内环氧化物合成酶2(Prostaglandin-endoperoxide Synthase 2,PTGS2)、丝裂原激活蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)3、MAPK8、JUN原癌基因(JUN)等多个靶点基因实现对肿瘤坏死因子(Tumor Necrosis Factor,TNF)、MAPK、核转录因子-κB(Nuclear Transcription Factor-κB,NF-κB)等多条信号通路的调控以发挥功效,为相关科研的进一步研究提供了理论依据。

Objective:To explore the action mechanism of the Longdan Xiegan decoction(龙胆泻肝汤)in the treatment of atopic dermatitis by network pharmacology.Methods:The effective components and action targets of the Longdan Xiegan decoction were mined in TCMSP database and BATMAN-TCM database to screen out disease targets by CTD database.The protein-protein interaction network of the intersection targets of drugs and disease was constructed.Cytoscape 3.7.2 was used to construct a four-dimensional network of disease-drug-target-gene.DAVID database was used to perform the GO function and KEGG pathway enrichment analysis on the targets.Finally,molecular docking verification was executed by AutoDock.Results:A total of 195 active components and 328 action targets were screened from the Longdan Xiegan decoction,among which 78 targets were closely related to atopic dermatitis.After screening,295 items were obtained by the GO functional enrichment analysis,and 86 signaling pathways were obtained by the KEGG pathway enrichment analysis.The molecular docking results showed that the compound active ingredients combined well with the core target.Conclusion:The Longdan Xiegan decoction mainly regulates multiple signaling pathways such as TNF,MAPK and NF-κB through the action of active compounds including quercetin,kaempferol and masterol on multiple target genes such as IL-6,PTGS2,MAPK3,MAPK8 and JUN.It provides a theoretical basis for the further related scientific research.