Integrating network pharmacology, transcriptomics, and experimental validation: Compound Baixianpi Formula targets IL-17A to inhibit dual PI3K-AKT/JAK2-STAT3 pathways for psoriasis improvement

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease. Existing therapies have limitations, necessitating the development of new treatment approaches. Compound Baixianpi Formula (FFBXP) is a clinically effective topical Chinese herbal formula, but its material basis and mechanism of action remain unclear. MATERIALS AND METHODS: FFBXP components were identified using UHPLC-Q-Orbitrap HRMS. Core targets and pathways were screened by integrating network pharmacology and transcriptomics analyses. The effects of FFBXP on skin lesions, histopathology, oxidative stress, and inflammatory mediators (IL-17A, IL-23, TNF-α) were evaluated using a IMQ mouse psoriasis model and a TNF-α-stimulated HaCaT cell model. Key mechanisms were validated through molecular docking, qRT-PCR, Western blot, and immunofluorescence techniques. RESULTS: Forty-two active components were identified in FFBXP. In vivo experiments demonstrated that FFBXP significantly improved erythema and skin lesion infiltration in psoriatic mice, while reducing levels of inflammatory cytokines (IL-17A, IL-23, TNF-α) and oxidative stress markers (MDA). In vitro experiments confirmed that FFBXP dose-dependently inhibited TNF-α-induced proliferation in HaCaT cells, reduced inflammatory cytokine levels, mitigated oxidative stress, and promoted apoptosis. Network pharmacology and transcriptomics analysis indicated its mechanism involves IL-17, PI3K-AKT, and JAK2-STAT3 signaling pathways. Molecular docking showed that six core active ingredients (berberine, resveratrol, quercetin, catechin, kaempferol, and osthol) had good binding activity with key target proteins. Further mechanism validation revealed FFBXP significantly decrease IL-17A expression and inhibited phosphorylation of downstream PI3K, AKT, JAK2, and STAT3 proteins. CONCLUSION: This study employs a combined strategy of network pharmacology, transcriptomics, and experimental validation to elucidate for the first time that FFBXP exerts its anti-psoriasis effects by targeting IL-17A and collaboratively inhibiting two key signaling pathways: PI3K-AKT and JAK2-STAT3.