基于网络药理学、分子对接和实验验证探讨参苓白术颗粒治疗特应性皮炎的作用机制  

Mechanism of Action of Shenling Baizhu Granule in Treatment of Atopic Dermatitis:A Study Based on Network Pharmacology,Molecular Docking,and Experimental Validation

作　　者：姜瀚 陈金润 王倩雯 张虹亚[1] JIANG Han;CHEN Jinrun;WANG Qianwen;ZHANG Hongya(The First Affiliated Hospital of Anhui University of Chinese Medicine,Anhui Hefei 230031,China)

机构地区：[1]安徽中医药大学第一附属医院,安徽合肥230031

出　　处：《安徽中医药大学学报》2025年第1期96-102,共7页Journal of Anhui University of Chinese Medicine

基　　金：国家重点研发计划项目(2018YFC1705302);安徽高校协同创新项目(GXXT-2020-064);安徽省张虹亚名老中医工作室项目(皖卫办秘〔2016〕680号)。

摘　　要：目的通过网络药理学、分子对接和实验验证探讨参苓白术颗粒治疗特应性皮炎(atopic dermatitis,AD)的作用机制。方法通过TCMSP、Genecards数据库查询参苓白术颗粒中药成分与疾病靶点,将二者交集基因进行基因本体(gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路功能富集。构建“药物—疾病—通路”网络,筛选核心活性成分和核心靶点,分子对接对其进行可视化。设置5、10、20、40μmol/L浓度梯度的槲皮素,CCK-8法检测其对肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和干扰素-γ(interferon-gamma,IFN-γ)共刺激的HaCaT细胞活力的影响,筛选最佳给药浓度。Western blot法检测Jun原癌激酶(Jun kinase,JUN)/半胱天冬蛋白酶-3(cysteinyl aspartate specific proteinase-3,caspase-3)/前列腺素内过氧化物合酶2(prostaglandin G/H synthase 2,PTGS2)蛋白表达水平。结果参苓白术颗粒治疗AD的主要通路有IL-17、TNF信号通路,其可能是通过核心活性成分槲皮素、木犀草素和山柰酚与核心靶点PTGS2、RXRA、RELA发挥治疗作用。CCK-8结果表明,HaCaT细胞生长受到抑制,其中槲皮素浓度在40μmol/L时,对细胞的抑制率约为50%。Western blot结果表明,40μmol/L槲皮素干预后,JUN和PTGS2蛋白表达水平升高,caspase-3蛋白表达水平降低(P<0.05)。结论参苓白术颗粒核心活性成分槲皮素可能通过降低caspase-3的表达水平,升高JUN和PTGS2的表达水平,发挥对皮肤组织的保护作用。Objective To investigate the mechanism of action of Shenling Baizhu Granule in the treatment of atopic dermatitis(AD)based on network pharmacology,molecular docking,and experimental validation.Methods TCMSP and Genecards databases were used to obtain the traditional Chinese medicine components of Shenling Baizhu Granule and the targets of the disease,which were intersected for gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.A drug-disease-pathway network was constructed,the core active components and targets were obtained,and molecular docking was used for visualization.Quercetin was used at a concentration gradient of 5,10,20,and 40μmol/mL,and CCK-8 assay was used to observe its effect on the viability of HaCaT cells co-stimulated by tumor necrosis factor-αand interferon gamma and identify the optimal concentration for administration.Western blot was used to measure the protein expression levels of Jun kinase(JUN),cysteine aspartic acid-specific protease 3(caspase-3),and prostaglandin G/H synthase 2(PTGS2).Results The IL-17 and TNF signaling pathways were the main pathways involved in the treatment of AD by Shenling Baizhu Granule,which might exert a therapeutic effect through the core active components of quercetin,luteolin,and kaempferol and the core targets of PTGS2,RXRA,and RELA.CCK-8 assay showed that the growth of HaCaT cells was inhibited,with an inhibition rate of about 50%at the concentration of quercetin of 40μmol/mL.Western blot showed that after intervention with 40μmol/mL quercetin,there were significant increases in the protein expression levels of JUN and PTGS2 and a significant reduction in the protein expression level of caspase-3(P<0.05).Conclusion As the core active component of Shenling Baizhu Granule,quercetin may exert a protective effect on skin tissue by inhibiting the expression of caspase-3 and promoting the expression of JUN and PTGS2.

关 键 词：参苓白术颗粒 特异性皮炎 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]