Dihydroartemisinin attenuates pemphigus vulgaris by regulating Dsg3 and the TLR9/NF-κB pathway.

OBJECTIVE

To evaluate the therapeutic efficacy of dihydroartemisinin (DHA) in pemphigus vulgaris (PV).

METHODS

Based on network pharmacology analysis, the TLR9/NF-κB signaling axis was selected as the primary pathway of interest. Skin specimens were first validated using immunohistochemistry. Subsequently, HaCaT cells were incubated. Desmoglein 3 (Dsg3) expression was detected using immunofluorescence staining. Cell viability was evaluated using MTS assay. The expression levels of TLR9, TRAF6, MyD88, p-NF-κB p65, MMP-9, and ADAM10 in HaCaT cells treated with control IgG (C-IgG), PV-IgG, and DHA were then examined by western blotting. Finally, these indicators were evaluated in Kunming mice. The results demonstrated that DHA suppressed PV-IgG - induced Dsg3 internalization and depletion. PV-IgG appeared to activate the NF-κB pathway through TLR9/TRAF6 signaling, while DHA effectively inhibited this effect. Moreover, DHA downregulated the expression of ADAM10 and MMP-9, critical proteases involved in the pathogenesis of PV.