Psoriasis is a common, chronic, inflammatory skin disease that affects many patients and exerts a heavy physical and mental burden. Wogonin (WG), derived from the root extract of Scutellaria Baicalensis, has shown therapeutic effects in a variety of inflammatory diseases. However, its specific effects and mechanisms in psoriasis treatment remain poorly understood. This study aimed to investigate the therapeutic effects and underlying mechanisms of WG in psoriasis. In this study, we first identified potential therapeutic targets of WG for psoriasis by intersecting the corresponding targets of psoriasis and WG, then performed Protein-Protein Interaction (PPI) network analysis and enrichment analyses. Next, we employed Cytoscape to identify potential key targets and performed molecular docking to predict possible targets. M5-induced HaCaT cells and imiquimod (IMQ)-mouse models were used to explore the effects and mechanisms. Bioinformatic analyses indicated that WG may exert anti-inflammatory effects through inhibiting PI3K/AKT pathway activation and oxidative stress. In vitro results showed that WG suppressed the increase of pro-inflammatory cytokine expression levels, reactive oxygen species (ROS) level, phosphorylation of Akt and p65, and several key target mRNA expression levels induced by M5 stimulation. Oral administration of WG remarkably alleviated psoriatic like lesions in IMQ-induced mice, inhibited inflammatory cytokines and Ki-67 expression level in mouse skin lesions. Our results indicate that WG exhibits significant anti-inflammatory effects in psoriasis by suppressing reactive oxygen species (ROS) production and inhibiting the AKT/NF-κB signaling pathway. These results highlight WG's potential as a promising therapeutic agent for psoriasis treatment.
