Hesperidin inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice by suppressing Th17 activity

Hesperidin (previously called vitamin P) is a predominant flavanone present in citrus fruits, and is presumed to have a role in their beneficial effect for human health because it possesses various physiological activities. In this study, we investigated the anti-allergic and anti-inflammatory effects of hesperidin and α-glucopyranosyl (αG)-hesperidin, its derivative with enhanced water-solubility, in NC/Nga mice, a human-like mouse model of atopic dermatitis. NC/Nga mice were fed a 0.1% αG-hesperidin or hesperidin diet for 8 weeks. αG-hesperidin and hesperidin feeding effectively inhibited skin lesions and immunoglobulin E (IgE) elevation. At the end of the 8-week-experimental period, the production of inflammatory cytokine interleukin (IL)-17 and interferon-gamma (IFN-γ) from splenocytes was lower in the αG-hesperidin/hesperidin-fed group than in the control group. Changes in mRNA expression in splenocytes are also examined using DNA microarray and real-time RT-PCR. It was revealed that cytotoxic T-lymphocyte antigen 4 (CTLA4), a regulatory T-cell (Treg) marker, was markedly upregulated in splenocytes, particularly by αG-hesperidin feeding. These results suggest that αG-hesperidin attenuated exacerbation of AD-like symptoms, decreased systemic immune hyper-responsiveness in part through the reduction of IgE, IL-17 and IFN-γ, and also modulated Th17/Treg balance in NC/Nga mice. Therefore, αG-hesperidin may be useful in the management of Th17-mediated allergic disorders.