Wogonin as a potential therapeutic agent for psoriasis: Core target identification and validation

Wogonin exhibits therapeutic effects in various skin diseases. However, the pharmacological effects and mechanisms of wogonin against psoriasis remain unclear. In the present study, the potential targets of wogonin were predicted and disease-related targets were obtained using Gene Expression Omnibus datasets. Intersection targets were identified using Venny 2.1.0 software, followed by input into the Search Tool for the Retrieval of Interacting Genes/Proteins database to generate a drug-target-disease visual network using Cytoscape 3.10.1. Core targets were obtained by protein-protein interaction analysis and the intersection targets were enriched through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The binding of wogonin to its core targets was evaluated using molecular docking. Furthermore, a psoriasis mouse model was constructed to assess the therapeutic effect of wogonin on skin lesions, and core targets of wogonin were verified by immunohistochemistry, including cyclin-D1 (CCND1), matrix metalloproteinase-9 (MMP9), cyclin-B1, cyclin-A2 (CCNA2), cyclin-dependent kinase 1 and androgen receptor. Molecular docking analysis revealed interactions between wogonin and these targets. <i>In vivo</i> results demonstrated that wogonin alleviated psoriasis-like lesions in the mouse model. Immunohistochemical and RNA sequencing analyses results suggested that MMP9, CCNA2 and CCND1 may be the key targets of wogonin in psoriasis. In conclusion, the findings of the present study suggested that wogonin may be a promising therapeutic candidate for psoriasis, potentially exerting its effects through the modulation of multiple molecular targets, including MMP9, CCNA2 and CCND1.