Integrating network pharmacology and experimental validation to elucidate the mechanism of Xiao-bi decoction in psoriasis treatment: Inhibition of JAK2/STAT3 signaling and rebalancing Th17/Treg responses.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal medicine called Xiao-bi decoction (XBD) has been used for decades to treat psoriasis, but its mechanism of action is poorly understood. AIM OF THE STUDY: To investigate the underlying mechanism of XBD against psoriasis using systematic pharmacological techniques. MATERIALS AND METHODS: A psoriasis model was established in mice using imiquimod (IMQ). The efficacy of XBD was evaluated based on psoriasis severity scores and immune cell infiltration. Core components and targets were screened using UPLC-QE-MS/MS and network pharmacology. The mechanism was further explored via transcriptome sequencing, ELISA, western blotting, immunolocalization, and molecular docking. RESULTS: XBD treatment significantly alleviated IMQ-induced psoriatic symptoms like erythema, scaling, and thickening. It reduced CD4T cell infiltration in skin and decreased serum levels of IL-17, IL-1β, IL-23, and IL-36. XBD specifically decreased CD4-IL-17cells while increasing CD4-FoxP3cells in both blood and skin. A total of 1223 chemical components were identified in XBD, including 78 blood-entering components. Network pharmacology and transcriptome analysis collectively demonstrate that XBD inhibits the activation of the JAK2/STAT3 signaling pathway, indicating its potential role in modulating this pathway. Our results also showed that XBD modulated Th17/Treg balance in serum and ameliorating skin inflammation in IMQ-induced psoriatic model. CONCLUSION: The herbal medicine Xiao-bi decoction may regulate the JAK2/STAT3 pathway, thereby influencing the Th17 response and Treg differentiation, and thereby alleviating the skin inflammation of psoriasis.