Anti-atopic dermatitis effects of dictamni cortex: Studies on in vitro and in vivo experimental models

Dictamni Cortex (DC), a Chinese herbal medicine with wind dispelling and itchiness relieving effects, is the most popular single herb prescribed for the treatment of atopic dermatitis (AD), as it is used in up to 12.68% of all herbal prescriptions for AD. The present study aimed to evaluate the anti-AD effect of Dictamni Cortex extract (DCE) and elucidate the underlying molecular mechanisms of its action using the 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like mouse model and a relevant in vitro experimental model. Female Balb/c mice were sensitized with 200 μl 0.5% DNCB for three days. After sensitization, mice were challenged with 200 μl 1% DNCB on the same dorsal skin and also 20 μl 1% DNCB on each ear every 3 days, and orally administrated by gavage with DCE (0.6, 1.2 and 2.4 g/kg) daily from day 14 to day 29 for 16 consecutive days. At the end of experiment, the clinical scores for AD on the mice were calculated to evaluate the therapeutic effect of DCE; and serum, ears and dorsal skin of the mice were collected for mechanistic study. The anti-allergic activity of DCE was also evaluated using antigen-induced RBL-2H3 cell line. The release of selected cytokines, chemokines and β-hexosaminidase was measured to determine the anti-allergic activity of DCE. In addition, intracellular Ca2+ level, MAPKs and Lyn phosphorylations were further investigated to reveal its anti-allergic molecular mechanisms. Our results demonstrated that DCE could markedly improve the AD-like symptoms in AD-like mice by inhibiting the mast cell infiltration, suppressing the production of Th2-associated cytokine (IL-4) and pro-inflammatory cytokines (TNF-α), and enhancing the protein expression of filaggrin through inhibition of the MAPKs and NF-κB pathways. Moreover, DCE suppressed mast cell degranulation through decreasing the intracellular Ca2+ level and inactivation of Lyn, Syk and PLCγs, suggesting DCE could regulate mast-cell-mediated allergic response. Our experimental results unambiguously indicate that DCE possesses potent anti-allergic effect, and help place the application of DC for the treatment of AD on a scientific footing.