Jiu-Wei-Yong-An Formula suppresses JAK1/STAT3 and MAPK signaling alleviates atopic dermatitis-like skin lesions

Abstract

Ethnopharmacological relevanceJiu-Wei-Yong-An (JWYA) formula is a traditional Chinese medicine (TCM) prescription used to treat atopic dermatitis (AD) in the clinic. JWYA is considered to have anti-inflammatory and antipruritic properties. However, the mechanism of JWYA remains unclear.Aim of the study: This study aimed to investigate the effect of JWYA on an experimental mouse AD model. Materials and methodsMice were sensitized with 2,4-dinitrochlorobenzene (DNCB) and intragastrically administered with JWYA for 14 days. The therapeutic effect was assessed using a grade four dermatitis score, skin moisture, thickness measurements, and a mouse behavior tests. H&E and toluidine blue staining were used to observe epidermal inflammatory thickening and mast cells in mouse skin lesions. Serum IgE levels and skin TNF-α and IL-4 levels were determined using ELISAs. The TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ mRNA expression levels in skin lesions were detected using qPCR. Network pharmacology analysis based on serum active components was performed to elucidate the mechanism, and the results were verified by Western blotting. Finally, we tested the binding affinity between the active ingredients of JWYA and JAK1 via molecular docking. ResultsJWYA improved the skin lesions of AD mice, relieved itching and reduced skin thickening. Additionally, JWYA decreased the serum IgE level and the levels of TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ in skin. Moreover, JWYA inhibited the activation of JAK1/STAT3 and MAPK (p38, ERK, and JNK) signaling. Molecular docking showed that kaempferol, luteolin, and forsythin have high affinity for JAK1. ConclusionsJWYA alleviates AD-like skin lesions and inhibited inflammation and skin itch. The effect of JWYA is attributed to blocking the JAK1/STAT3 and MAPK signaling pathways. We suggest that JWYA may be an alternative therapy for the treatment of AD.