Caffeoyl\u2013Pro\u2013His amide relieve DNCB-Induced Atopic Dermatitis-Like phenotypes in BALB/c mice

Sunhyae Jang,Chan Yeong Heo,Ji Won Kim,Kyu Han Kim,Jungyoon Ohn,Yoon-Sik Lee,Dasom Jeon,So Min Kang,Ohsang Kwon

doi:10.1038/s41598-020-65502-2

Abstract

The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress influences these factors, antioxidant agents may be effective candidates in the treatment of AD. To evaluate the effect of Caffeoyl–Pro–His amide (CA-PH), an antioxidant agent, on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice. Topical sensitization and challenge by DNCB were performed on the dorsal skin of BALB/c mice to induce AD-like cutaneous lesions, phenotypes, and immunologic response. CA-PH was applied topically for 2 weeks to assess its effects on DNCB-induced AD-like phenotypes. As a result, CA-PH relieved DNCB-induced AD-like phenotypes quantified by dermatitis severity score, scratching duration, and trans-epidermal water loss. Histopathological analysis showed that CA-PH decreased epidermal thickening, the number of mast cells, and eosinophil infiltration in dermis. Immunohistochemical staining revealed that CA-PH recovered skin barrier-related proteins: filaggrin, involucrin, and loricrin. As for the immunologic aspects, CA-PH treatment lowered mRNA or protein levels of interleukin (IL)-4, IL-6, IL-17a, IL-1b, IL-31, and IL-33 levels and thymic stromal lymphopoietin (TSLP) levels in cutaneous tissue, reducing the DNCB-induced serum IgE level elevation. In conclusion, topical CA-PH may be a therapeutic option for the treatment of AD.

Highlights

Atopic dermatitis (AD) is a pruritic cutaneous inflammatory disorder with chronic recurrence
We evaluated the effect of Caffeoyl–Pro–His amide (CA-PH) on the 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like phenotypes in BALB/c mice
On Day 28, the dorsal skins of mice applied with DNCB and vehicle showed prominent erythema, edema/papulation, excoriation, and scaling/dryness compared to the control group (Fig. 3a,b), indicating that DNCB efficiently induced AD-like phenotypes

Summary

Introduction

Atopic dermatitis (AD) is a pruritic cutaneous inflammatory disorder with chronic recurrence. The increased TSLP expression has been attributed to the pathogenesis of AD15 In this context, reducing ROS in the cutaneous tissue may be an efficient strategy to regulate the three major factors of AD pathogenesis and alleviate AD-associated phenotypes. Kwak et al developed a conjugated peptide form of caffeic acid, caffeoyl-prolyl-histidine amide (Fig. 1 CA-L-Pro-L-His-NH2; CA-PH), to enhance anti-oxidative property with sufficient stability[18,19]. Proline in this conjugated form enhances the antioxidant effect, while the imidazole ring of histidine optimizes the effect. We evaluated the effect of CA-PH on the 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice

Methods

Results

Conclusion