Wikstroemiaganpi Extract Improved Atopic Dermatitis-Like Skin Lesions via Suppression of Interleukin-4 in 2,4-Dinitrochlorobenzene-Induced SKH-1 Hairless Mice

Abstract

Plants of the genus Wikstroemia are used in Chinese traditional medicine to treat inflammatory diseases, such as arthritis, bronchitis, and pneumonia. The present study was designed to determine whether Wikstroemia ganpi (Siebold and Zucc.) Maxim. offers a potential means of treating 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Symptoms such as redness, edema, and keratinization in AD mice induced by DNCB were alleviated by the co-application of an ethanolic extract of W. ganpi for 2 weeks. The severity of skin barrier function damage was evaluated by measuring TEWL (transepidermal water loss). TEWLs of DNCB sensitized mouse dorsal skin were reduced by the application of a W. ganpi ethanolic extract, and skin hydration was increased. In addition, the infiltration of inflammatory cells into the dermis was significantly reduced, as were blood levels of IgE and IL-4, which play an important role in the expression of AD. The results of this experiment suggest that W. ganpi is a potential therapeutic agent for AD.

Keywords: 2,4-dinitrochlorobenzene; Wikstroemia ganpi; atopic dermatitis; immunoglobulin E; interleukin-4.

Figure 1

Effects of W. ganpi EtOH extract (WGE) on the development of Atopic dermatitis (AD)-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in the dorsal skin of the SKH-1 hairless mice. (a) Summarized diagram of the experiment schedule; (b) Clinical change of the AD-like skin lesion; (c) Dermatitis score. CON: control group, DNCB: DNCB-treated group, W. ganpi: DNCB and 1% W. ganpi EtOH extract-treated group, Elidel: DNCB and Elidel cream treated group. ^# p < 0.05 vs. the CON group; * p < 0.05 vs. the DNCB group.

Figure 2

Effects of WGE on the change of the epidermal thickness in AD-like symptoms induced by DNCB in hairless mice. (a) Results of changes in epidermal thickness of skin lesions confirmed by histopathological examination. Stained by Hematoxylin and eosin (H&E) staining; (b) Epidermal thickness. CON: control group, DNCB: DNCB-treated group, W. ganpi: DNCB and 1% W. ganpi EtOH extract-treated group, Elidel: DNCB and Elidel cream treated group. ^# p < 0.05 vs. the CON group; * p < 0.05 vs. the DNCB group.

Figure 3

Effects of WGE on the change of the number of mast cells per dermis in AD-like symptoms induced by DNCB in hairless mice. (a) Results of changes in the number of the mast cells per dermis of skin lesion determined by histopathological examination. Stained by toluidine blue; (b) The number of mast cells per dermis. CON: control group, DNCB: DNCB-treated group, W. ganpi: DNCB and 1% W. ganpi EtOH extract-treated group, Elidel: DNCB and Elidel treated group. ^# p < 0.05 vs. the CON group; * p < 0.05 vs. the DNCB group.

Figure 4

Effects of WGE on the serological change of the IL-4 and IgE concentration in AD-like symptoms induced by DNCB in hairless mice. (a) Serum total IgE levels; (b) Serum total IL-4 levels. ^# p < 0.05 vs. the CON group; * p < 0.05 vs. the DNCB group.

Figure 5

Effects of WGE on the relative gene expression of cytokines TNF-α, IFNγ, and IL-4 DNCB sensitized mouse dorsal skin. (a) The mRNA expression of TNF-α; (b) The mRNA expression of IFNγ; (c) The mRNA expression of IL-4 ^# p < 0.05 vs. the CON group; * p < 0.05 vs. the DNCB group.

Figure 6

Effects of WGE on the skin barrier function in AD-like symptoms induced by DNCB in hairless mice. (a) Transepidermal water loss (TEWL); (b) Skin hydration value. ^# p < 0.05 vs. the CON group; * p < 0.05 vs. the DNCB group.

Figure 7

HPLC-PDA chromatograms of WGE at 340 nm (a) and chemical structure (b). Peaks: (1) 4-methoxyluteolin-5-O-glucoside; (2) quercitrin; (3) pilloin 5-O-β-d-glucopyranoside; (4) triumbelletin; (5) daphnoretin.