Network Pharmacology and Molecular Docking-Based Approach to Explore Potential Bioactive Compounds from on Chemokine Signaling Pathways in the Treatment of Psoriasis Disease.

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and dysregulated chemokine signaling. (KP) has long been valued for its medicinal properties; however, its specific role in psoriasis treatment remains unclear. This study investigates the anti-psoriatic potential of methoxyflavones derived from KP through an integrated approach combining network pharmacology, molecular docking, and experimental validation. A total of 232 target genes were identified as being associated with KP bioactive compounds, of which 64 overlapped with psoriasis-related genes implicated in chemokine signaling pathways. Molecular docking analyses revealed that key methoxyflavones interact with pivotal proteins such as protein kinase B (AKT1 or AKT), proto-oncogene tyrosine-protein kinase (SRC), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), suggesting their potential involvement in modulating inflammation. Experimental results confirmed that 5,7,4'-trimethoxyflavone and 3,5,7-trimethoxyflavone significantly inhibited keratinocyte proliferation, migration, and macrophage activation, key processes in psoriasis progression. Additionally, both compounds reduced nitric oxide production, supporting their anti-inflammatory effects. Western blot analysis further demonstrated that these compounds tended to decrease the phosphorylation levels of AKT and SRC, supporting their role in influencing inflammatory signaling pathways. These findings suggest that methoxyflavones from KP act through multi-target mechanisms, offering potential as natural therapeutic agents for psoriasis. Further, in vivo studies are needed to validate their efficacy and explore their clinical applications.