A pectic polysaccharide from Lonicera japonica alleviates DNCB-induced atopic dermatitis-like inflammation associated with gut microbial and metabolic alterations and reduced cutaneous JAK2/STAT3 activation and Th17 responses.
TL;DR
Findings indicate that oral WLJP-025p treatment is associated with concurrent intestinal and cutaneous changes in this AD-like model, and exerted protective effects against DNCB-induced AD-like dermatitis.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Lonicera japonica Thunb. (Jin Yin Hua) is a traditional medicinal herb widely used in East Asia for inflammatory disorders and is commonly included in herbal prescriptions for atopic dermatitis (AD). WLJP-025p, a homogeneous pectic polysaccharide isolated from Lonicera japonica, has shown anti-inflammatory and anti-AD potential, but its underlying mechanisms remain unclear.
Aim
OF THE STUDY This study aimed to evaluate the therapeutic effect of WLJP-025p on DNCB-induced AD-like dermatitis in mice and to investigate associated changes in epidermal barrier dysfunction, Th17/IL-17A-associated inflammation, JAK2/STAT3 signaling, and gut microbial and metabolic profiles.
Materials And Methods
An AD-like mouse model was established in BALB/c mice by repeated application of 2,4-dinitrochlorobenzene (DNCB). WLJP-025p was orally administered at 30 or 60 mg/kg during the challenge phase, and topical dexamethasone was used as a reference anti-inflammatory control. Disease severity was assessed by skin appearance, dermatitis score, ear thickness, serum biomarkers, and histopathological examination. Skin barrier and inflammation-related proteins were evaluated by immunohistochemistry, immunofluorescence, Western blotting, and flow cytometry. Colonic injury was examined by hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining. Fecal metagenomic and metabolomic analyses were conducted to characterize gut microbial and metabolic changes.
Results
WLJP-025p significantly alleviated DNCB-induced AD-like lesions, as evidenced by reduced erythema, scaling, excoriation, ear swelling, dermatitis scores, epidermal hyperplasia, and mast cell infiltration. WLJP-025p decreased serum IgE, IL-1β, IL-6, and IL-17A levels. It restored filaggrin (FLG) expression and suppressed thymic stromal lymphopoietin (TSLP) expression in skin lesions, indicating improved epidermal barrier function. WLJP-025p also reduced the proportions of splenic CD3+CD4+IL-17A+ T cells and suppressed cutaneous IL-17A-related inflammatory mediators, including CCR6 and CCL20. These changes were accompanied by decreased phosphorylation of JAK2 and STAT3 in lesional skin. In addition, WLJP-025p alleviated DNCB-associated colonic injury and was accompanied by changes in gut microbial and metabolic profiles.
Conclusion
WLJP-025p exerted protective effects against DNCB-induced AD-like dermatitis. Treatment was accompanied by restoration of epidermal barrier-related markers, reduced JAK2/STAT3 activation and Th17/IL-17A-associated inflammatory signaling, improved gut barrier integrity, and alterations in gut microbial and fecal metabolite profiles. These findings indicate that oral WLJP-025p treatment is associated with concurrent intestinal and cutaneous changes in this AD-like model.