A homogeneous Lonicera japonica polysaccharide alleviates atopic dermatitis by promoting Nrf2 activation and NLRP3 inflammasome degradation via p62

Lonicera japonica Thunb. is a traditional medicinal herb with a long history owing to its widespread use in Asia for the treatment of several inflammatory diseases including allergic dermatitis; however, its active components and mechanism of action have not been fully elucidated.In this study, a homogeneous polysaccharide with strong anti-inflammatory effects was extracted from the traditional Chinese medicine Lonicera japonica. The mechanism by which the polysaccharide WLJP-025p regulates p62 to activate Nrf2, promote NLRP3 inflammasome degradation, and improve AD was investigated.An AD model was established using DNCB, and saline was used as a control. The WLJP-L and WLJP-H groups were administered 30 and 60 mg/kg WLJP-025p during the model challenge period, respectively. The therapeutic effect of WLJP-025p was evaluated by determining the skin thickness, performing HE and toluidine blue staining, detecting TSLP via IHC, and determining serum IgE and IL-17 levels. Th17 differentiation was detected using flow cytometry. IF and WB were performed to evaluate the expression levels of c-Fos, p-p65, NLRP3 inflammatory bodies, autophagy pathway, ubiquitination, and Nrf2 proteins.WLJP-025p significantly inhibited DNCB-induced skin hyperplasia and pathological abnormalities and increased TSLP levels in mice. The differentiation of Th17 in the spleen, IL-17 release, p-c-Fos, p-p65 protein expression, and NLRP3 inflammasome activation in the skin tissues were reduced. Furthermore, p62 expression, p62 Ser403 phosphorylation, and ubiquitinated proteins were increased.WLJP-025p improved AD in mice by upregulating p62 to activate Nrf2 and promote the ubiquitination and degradation of NLRP3.