基于网络药理学、分子对接技术及动物实验的苦参外治湿疹作用机制研究OA

Objective:To investigate the mechanism of Kushen external treatment for eczema using network pharma-cology,molecular docking technology and animal experiments.Methods:The active components and targets of Kushen as well as eczema disease targets were screened using the TCMSP and GeneCards databases.Overlapping targets between the herb and the disease were identified.A protein-protein interaction(PPI)network and a"Kushen-active component-eczema target"network were constructed.Key targets and pathways involved in the Kushen external treatment for eczema were ob-tained through Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Molecular docking was performed between core components and key targets.A mouse eczema model was established to further verify the anti-inflammatory effect of Kushen.Results:A total of 42 active components of Kushen were identified,including 4 key components,along with 177 targets of the herb,3925 eczema-related targets,and 89 overlapping targets.Comprehensive analysis of the PPI network and the"Kushen-active component-eczema"target net-work indicated that the mechanism of Kushen external treatment for eczema involved targets such as serine/threonine kinase(Akt-1),mitogen-activated protein kinase 14(MAPK14),interleukin-6(IL-6),interleukin-1β(IL-1β),and interleukin-10(IL-10).GO function and KEGG enrichment analyses revealed that multiple pathways,including IL-17,PI3K-Akt,NF-κB,and JAK-STAT,might play a role in the Kushen external treatment for eczema.Molecular docking confirmed that Akt1 and IL-6 had a high binding affinity and stable binding with the core components of Kushen.Animal experiments further demonstrated that wet compresses of Kushen reduced serum levels of pro-inflammatory factors IL-1β and IL-6,increased the level of anti-inflammatory factor IL-10,and alleviated the degree of skin inflammation in eczema model mice,likely through modulation of the PI3K-Akt pathway.Conclusion:External application of Kushen can act on multiple cytokines and chemokines through various receptor signaling pathways and immune pathways,thereby regulating immunity,suppressing inflammatory responses,and improving the skin lesion status in eczema.