广东药科大学学报2024，Vol.40Issue(2)：91-103,13.DOI:10.16809/j.cnki.2096-3653.2023120601
基于网络药理学探讨绿原酸治疗特异性皮炎的作用机制
Study on mechanisms of chlorogenic acid in treating atopic dermatitis based on network pharmacology
摘要
Abstract
Objective To investigate the targets and potential mechanisms of chlorogenic acid(CGA)in the treatment of atopic dermatitis(AD)based on network pharmacology,molecular docking technology and experimental validation.Methods STITCH,SwissTargetPrediction and PharmMapper databases were used to predict and screen the corresponding targets of CGA.Targets corresponding to AD were collected and screened from the DisGeNET,OMIM,and GendCards databases.The Venny 2.1.0 online tool was used to obtain the intersection targets of CGA and AD.The intersecting targets were constructed by using the STRING 11.5 database to construct the protein interaction(PPI)network diagram,and the PPI network diagram was visualized and analyzed by Cytoscape 3.10.0 software,and the core targets were screened by the CytoNCA plug-in.The DAVID platform was used for GO and KEGG enrichment analysis,and the key ways of CGA in the treatment of AD were discussed,and the binding affinity between CGA and core targets was evaluated by molecular docking.An AD model was established for 2,4-dinitrochlorobenzene(DNCB)-induced mice,and the results of network pharmacology prediction were verified by dermatitis score,spleen index,pathological staining and RT-qPCR.Results A total of 241 targets of CGA and 1 450 targets of AD were screened,and a total of 69 intersecting targets were obtained.Among them,13 core targets were identified through PPI network topology analysis,including MMP9,HSP90AA1,HRAS,NOS2 and RHOA,and molecular docking showed that CGA had strong binding to these core targets.KEGG pathway enrichment analysis showed that TNF signaling pathway,lipid and atherosclerosis,VEGF signaling pathway and other intersecting targets were significantly enriched.In vivo studies showed that CGA effectively reduced epidermal thickness,dermatitis score and spleen index compared with the model group.RT-qPCR results showed that CGA significantly reduced the expression of MMP9 and HSP90AA1 mRNA,and reduced the expression of TNF-α,TNFR1 and AKT1 genes related to TNF signaling pathway.Conclusion CGA can effectively improve AD symptoms by regulating TNF signaling pathway,which provides a reference for subsequent research and development.关键词
网络药理学/分子对接/特异性皮炎/绿原酸/TNF信号通路/机制Key words
network pharmacology/molecular docking/atopic dermatitis/chlorogenic acid/TNF signaling pathway/mechanism分类
医药卫生引用本文复制引用
聂文凯,徐颖,于宗睿,杨慧文,刘冰,王桂香..基于网络药理学探讨绿原酸治疗特异性皮炎的作用机制[J].广东药科大学学报,2024,40(2):91-103,13.基金项目
国家自然科学基金面上项目(81873225) （81873225）
国家大学生创新创业训练项目(202310573012) （202310573012）
