Paedoksan ameliorates allergic disease through inhibition of the phosphorylation of STAT6 in DNCB-induced atopic dermatitis like mice

Various allergic diseases such as atopic dermatitis (AD), allergic rhinitis, and asthma are considered incurable conditions that have yet to be fully conquered. Paedoksan (PDS), an herbal preparation consisting of 14 medicines, displays effective anti-inflammatory and anti-allergic properties, yet its underlying molecular mechanism is unknown. This study aims to uncover PDS's mechanism for treating allergic diseases and suggest its therapeutic potential. Through a network pharmacological prediction, its impact on signal transducer and activator of transcription 6 (STAT6) regulation, a sub-mechanism of interleukin 4 (IL-4), a major inflammatory cytokine involved in degranulation and allergy, was investigated in RBL-2H3 cells and an atopic mouse model. PDS inhibits immunoglobulin E (IgE)-induced degranulation and STAT6 phosphorylation evoked by IL-4 in granulocytes. The downregulation of phospho-STAT6 and thymic stromal lymphopoietin (TSLP) by PDS was confirmed in 2,4-dinitrochlorobenzene (DNCB)-induced mouse skin. The results demonstrate that PDS exhibited remarkable effects on degranulation and STAT6 phosphorylation in RBL-2H3 cells, as well as in an atopic mouse model. Furthermore, the main active components from PDS based on chromatographic analysis showed good accordance with PDS's effects on RBL-2H3 cells. In summary, these findings collectively suggest that PDS holds the potential to effectively suppress inflammatory and allergic reactions by obstructing the target IL-4 protein and its downstream effects, as elucidated through a network pharmacological analysis.