Effect of topical application of quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside on atopic dermatitis in NC/Nga mice
Introduction
Atopic dermatitis (AD) is the most common, relapsing allergic disease of the skin. It is characterized by pruritic and eczematous skin lesions. AD is caused by the complex interaction of genetic and environmental factors that result in immune system dysregulation [1]. In AD, type 2 helper T (Th2) cells show increased production of interleukin (IL)-4, which stimulates plasma cells to increase IgE production and promotes further Th2 cell development [2]. Other studies have shown that in addition to IL-4, IFN-γ production by Th1 cells at both mRNA and protein levels is induced in the lesions of AD patients [3], [4]. These reports suggest that both Th1 and Th2 subsets contribute to the pathogenesis of AD [5]. In addition to the Th1/Th2 paradigm, role of Th17 have been highlighted. Phenotypic analysis of peripheral blood mononuclear cells derived from AD patients exhibited a marked increase in the IL-17 + CD4+ T-cell population. A high percentage of IL-17-producing cells was found in severe AD, which suggests a direct correlation between the presence of Th17 cells and disease severity [6]. To date, AD has been regarded as an intractable dermatological disorder, whose treatment modalities consist mainly of corticosteroids, anti-histamines, and immune suppressants. However, these therapeutic agents are of limited value because of the frequent occurrence of adverse effects and recurrence after cessation of therapy. Therefore, alternative and compensatory agents need to be developed promptly to treat this condition. Recently, phytochemicals have been tested as potential therapeutic agents for the treatment of AD [7], [8], [9].
The flavonoid quercetin and its derivatives are known to exert several antioxidative [10], [11] and anti-inflammatory effects. Previous studies showed that quercetin inhibited proinflammatory cytokine expression through modulation of the activation of NF-kB in a human mast cell line [12] and downregulated eosinophil and IL-5 production in a murine model of asthma [13]. In addition, a study showed the inhibitory effect of quercetin and tannic acid on angiogenesis and TARC expression in NC/Nga mice [14].
Quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside(QGR) is a new quercetin derivative, and the effect of QGR on atopic dermatitis has not been studied, so we investigated the therapeutic anti-inflammatory and anti-immunologic effects of QGR on atopic dermatitis like skin lesion on NC/Nga mice.
Section snippets
Preparation of extraction and isolation of QGR
The 2 kg of the leaf of Acer ginnala collected from Korea National Arboretum (Pocheon, Korea) were extracted several times with 80% methanol at room temperature (for 72 h). After removing the acetone under vacuum, the aqueous solution was filtered through filter paper (Tokyo Roshi Kaisha Ltd, Tokyo, Japan). The filtrate was then concentrated (674 g) and applied to Sephadex LH-20 (2 kg, 10–25 μm, 10 × 80 cm, GE Healthcare Bio-Science AB, Uppsala, Sweden) eluted with water containing increasing
QGR inhibits production of NO in PGN-stimulated macrophage
To evaluate the effect of QGR on NO secretion in PGN stimulated RAW 264.7 cells, we measured nitrite concentrations in culture media using the Griess reagent. RAW264.7 cells were treated with 0–2 μg/ml QGR for 24 h and stimulated with PGN for 24 h. NO secretion was increased by treatment of PGN alone; QGR significantly reduced NO levels in PGN-stimulated cells in a dose-dependent manner (Fig. 2). Interestingly, treatment group of QGR resulted in similarly decreased NO secretion compared with that
Discussion
Atopic dermatitis (AD) is a highly pruritic inflammatory skin disease characterized by skin hypersensitivity in response to various environmental and genetic factors [1]. There are several treatments for AD. The currently used steroids, anti-histamines, and immunosuppressants have shown limitations in their efficacy, and it is therefore imperative that alternative and compensatory agents be developed promptly to treat this condition. To develop an appropriate treatment agent for AD using a
Acknowledgements
This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A091121).
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