Abstract
BackgroundLong-term use of most immunosuppressants to treat allergic contact dermatitis (ACD) generates unavoidable severe side effects, warranting discovery or development of new immunosuppressants with good efficacy and low toxicity is urgently needed to treat this condition. Hispidulin, a flavonoid compound that can be delivered topically due to its favorable skin penetrability properties, has recently been reported to possess anti-inflammatory and immunosuppressive properties. However, no studies have investigated the effect of hispidulin on Th1 cell activities in an ACD setting.MethodsA contact hypersensitivity (CHS) mouse model was designed to simulate human ACD. The immunosuppressive effect of hispidulin was investigated via ear thickness, histologic changes (i.e., edema and spongiosis), and interferon-gamma (IFN-γ) gene expression in 1-fluoro-2,4-dinitrobenzene (DNFB)-sensitized mice. Cytotoxicity, total number of CD4+ T cells, and percentage of IFN-γ-producing CD4+ T cells were also investigated in vitro using isolated CD4+ T cells from murine spleens.ResultsTopically applied hispidulin effectively inhibited ear swelling (as measured by reduction in ear thickness), and reduced spongiosis, IFN-γ gene expression, and the number of infiltrated immune cells. The inhibitory effect of hispidulin was observed within 6 h after the challenge, and the observed effects were similar to those effectuated after dexamethasone administration. Hispidulin at a concentration up to 50 μM also suppressed IFN-γ-producing CD4+ T cells in a dose-dependent manner without inducing cell death, and without a change in total frequencies of CD4+ T cells among different concentration groups.ConclusionThe results of this study, therefore, suggest hispidulin as a novel compound for the treatment of ACD via the suppression of IFN-γ production in Th1 cells.
Highlights
Long-term use of most immunosuppressants to treat allergic contact dermatitis (ACD) generates unavoidable severe side effects, warranting discovery or development of new immunosuppressants with good efficacy and low toxicity is urgently needed to treat this condition
Hispidulin-induced suppression of contact hypersensitivity (CHS) responses To evaluate the immunosuppressive effect of hispidulin on ACD, a CHS mouse model was designed using DNFB for sensitization and elicitation (Fig. 1a)
After hispidulin treatment of 30 μg/ear, ear edema and spongiosis were reduced to almost the same levels as those observed after dexamethasone application [DNFB (+)/His30 vs. DNFB (+)/Dex]
Summary
Long-term use of most immunosuppressants to treat allergic contact dermatitis (ACD) generates unavoidable severe side effects, warranting discovery or development of new immunosuppressants with good efficacy and low toxicity is urgently needed to treat this condition. No studies have investigated the effect of hispidulin on Th1 cell activities in an ACD setting. For treatment of ACD, topical and systemic administrations of immunosuppressive drugs, such as corticosteroids, cyclosporine-A and tacrolimus, are normally used. These drugs associated with various adverse effects after prolonged use [4,5,6], so it is of importance to find a novel candidate compound to treat ACD. Phytochemicals have become good candidate active compounds for drug discovery and for the development of novel immunosuppressive treatments for ACD due to their high efficacy and low toxicity. A number of reports showed that hispidulin suppressed inflammations in mouse models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema [9, 10], croton oil-induced
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