Panduratin A, an activator of PPAR-α/δ, suppresses the development of oxazolone-induced atopic dermatitis-like symptoms in hairless mice

Aims: Panduratin A isolated from Boesenbergia pandurata (Roxb.) has been reported to have antioxidant, anti-inflammatory, and anti-allergic activities. However, the effect of panduratin A on atopic dermatitis (AD) has not been studied. In the present study, we investigated the efficacy of panduratin A, an activator of peroxisome proliferator-activated receptors (PPAR) alpha/delta, using oxazolone-induced AD-like model in hairless mice. Main methods: To determine PPAR alpha/delta activation of panduratin A, HaCaT, Hs68, and COS-7 cells were treated with panduratin A, then PPAR alpha/delta and PPAR response element (PPRE) activities were assessed with a reporter gene assay. For the in vivo study, oral administration of panduratin A was performed for 4 weeks, with oxazolone treatment every other day. The efficacy of panduratin A on parameters of oxazolone-induced AD was assessed physiologically, morphologically, and immunologically. Key findings: Panduratin A increased PPAR sigma/delta and PPRE activation both in vitro and in vivo. Panduratin A attenuated dermatitis-associated barrier damage as demonstrated by transepidermal water loss, erythema, and filaggrin expression. Furthermore, infiltration of inflammatory cells and epidermal thickness in the skin were decreased. Panduratin A decreased serum immunoglobulin (Ig) E and interleukin-4 levels but increased IgG2a and interferon-gamma levels. In addition, panduratin A decreased inflammation-associated molecules in the skin. Panduratin A also decreased Th2-associated molecules and increased Thl /regulatory T cell (Treg)-associated molecules in the spleen. Significance: Panduratin A showed a beneficial effect on AD by modulating Thl/Th2/Treg-associated immune response and is a potential candidate for treating AD. (C) 2014 Elsevier Inc All rights reserved.