Osthole ameliorates chronic pruritus in 2,4-dichloronitrobenzene-induced atopic dermatitis by inhibiting IL-31 production

Objective: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis(AD), focusing on its ability to alleviate chronic pruritus(CP) and the underlying molecular mechanisms.Methods: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene(DNCB)-induced AD mouse model and tumor necrosis factor-a(TNF-a) and interferon-γ(IFN-γ) stimulated human immortalized epidermal(HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), western blot(WB), quantitative real-time PCR(qRT-PCR), and immunofluorescence staining.Results: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin(IL)-31 and IL-31 receptor A(IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65(p-p65) and phosphor-inhibitor of nuclear factor kappa-Ba(p-IKBa). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor a(PPARa) and PPARγ in HaCaT cells.Conclusion: These findings indicated that osthole effectively inhibited CP in AD by activating PPARa, PPARγ, repressing the NF-KB signaling pathway, as well as the expression of IL-31 and IL-31 RA.