Ann Dermatol.  2017 Feb;29(1):61-68. 10.5021/ad.2017.29.1.61.

Topical Application of Eupatilin Ameliorates Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

• Lee JH
• Lee YJ
• Lee JY
• Park YM

• KMID: 2368029
• DOI: http://doi.org/10.5021/ad.2017.29.1.61

Abstract

BACKGROUND
Atopic dermatitis (AD) is an inflammatory skin disorder with severe pruritus. Despite advancements in medicine, therapeutic treatments for AD are still limited. Eupatilin (5,7-dihydroxy-30,40,6-trimethoxyflavone) is one of the lipophilic flavonoids from Artemisia umbelliformis Lam. and Artemisia genipi Weber.
OBJECTIVE
Although it has been reported to act a role in improving inflammation, its action on AD is uncertain. In this study, we examined the role of eupatilin on AD-like skin lesions in NC/Nga mice.
METHODS
2,4-dinitrochlorobenzene was repeatedly applied to the ear of NC/Nga mice to produce AD-like skin lesions. Eupatilin (1%, once a day for 5 consecutive days/week) was applied topically for four weeks for the evaluation of its therapeutic effects.
RESULTS
1% eupatilin cream significantly reduced the clinical severity score of AD-like lesions, compared to the vehicle (p<0.005). A histopathological analysis revealed that 1% eupatilin cream significantly decreased the mast cell infiltration as well as inflammatory cell infiltration, compared to the vehicle (p<0.005). We showed that 1% eupatilin cream significantly reduced the expression of thymic stromal lymphopoietin, tumor necrosis factor-α, interleukin-4, and interleukin-19, but not interferon-γ, compared to the vehicle (p<0.005).
CONCLUSION
Considering the therapeutic reaction of eupatilin on AD-like lesions as in this study, the substance has a promising to be an adjuvant topical agent for the control of AD.

Keyword

Atopic dermatitis; Dermatitis; Eupatilin; Interleukin-4; NC/Nga mice

MeSH Terms

Animals
Artemisia
Dermatitis
Dermatitis, Atopic
Ear
Flavonoids
Inflammation
Interleukin-4
Mast Cells
Mice*
Necrosis
Pruritus
Skin*
Therapeutic Uses
Flavonoids
Interleukin-4
Therapeutic Uses

Figure

• 

  Fig. 1 Experimental design. DNCB: 2,4-dinitrochlorobenzene.

• 

  Fig. 2 (A) Photographs of the clinical features of NC/Nga mice non-treated (NT), 2,4-dinitrochlorobenzene (DNCB)+vehicle (VH), DNCB+1% eupatilin cream, DNCB+0.03% tacrolimus ointment, on day 29 following the first challenge. (B) Clinical skin severity scores. (C) Ear thickness. Photos and graphs revealed that 1% eupatilin cream significantly reduced the clinical signs such as erythema, edema, excoriation, and dryness on day 29, compared to the vehicle only (p<0.05). Data are presented as mean±standard error of the mean (n=5). *p<0.05, compared to the vehicle group.

• 

  Fig. 3 (A) Histological features of atopic dermatitis (AD)-like skin lesions after treatment with 1% eupatilin. 1% eupatilin cream significantly reduced inflammatory cell infiltration (p<0.05) (H&E, ×200) and also significantly reduced mast cell infiltration in the dermis, compared to the vehicle (p<0.05) (toluidine blue, ×200). (B) The epidermal thickness in five randomly chosen visual fields at ×200 magnification (H&E, ×200). (C) The number of mast cells in five randomly chosen visual fields at ×400 magnification (toluidine blue, ×400). Non-treated (NT), DNCB+vehicle (VH), DNCB+1% eupatilin cream, DNCB+0.03% tacrolimus ointment at day 29 following the first challenge. Data are presented as mean±standard error of the mean (n=5). *p<0.05, compared to the vehicle group.

• 

  Fig. 4 Effects of 1% eupatilin on mRNA expression of thymic stromal lymphopoietin (TSLP), tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-5, IL-13, IL-19, and interferon (IFN-γ) in the ears of NC/Nga mice. 1% eupatilin cream also significantly decreased the mRNA expression of TSLP, TNF-α, IL-4, and IL-19, but not of IL-5, IL-13, and IFN-γ, compared to the vehicle (p<0.05). Non-treated (NT), 2,4-dinitrochlorobenzene (DNCB)+vehicle (VH), DNCB+1% eupatilin cream, DNCB+0.03% tacrolimus ointment. Data are presented as mean±standard error of the mean (n=5). *p<0.05, compared to the vehicle (VH) group. RFI: relapse-free interval.

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