Immunomodulatory and Anti-inflammatory Effects of Asiatic Acid in a DNCB-Induced Atopic Dermatitis Animal Model.

Gyo-Ha Moon,Kwon-Jai Lee,Eun-Kyung Kim,Kang-Hyun Chung,Yonghyeon Lee,Jeung-Hee An

doi:10.3390/nu13072448

Abstract

We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5–20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1β and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.

Highlights

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with several symptoms, such as pruritus, erythema, swelling, and cracked skin [1]
T helper 1 (Th1) and Th2 cells are involved in eliciting a strong type 2 immune response, which plays an important role in AD; the immune response includes a significant increase in mast cell infiltration and levels of Th2-related cytokine and serum immunoglobulin (Ig) E [2]
This study aimed to evaluate the efficacy of immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in IFN-γ- and tumor necrosis factor (TNF)-α-treated HaCaT cells and DNCB-induced AD BALB/c mouse models

Summary

Introduction

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with several symptoms, such as pruritus, erythema, swelling, and cracked skin [1]. T helper 1 (Th1) and Th2 cells are involved in eliciting a strong type 2 immune response, which plays an important role in AD; the immune response includes a significant increase in mast cell infiltration and levels of Th2-related cytokine and serum immunoglobulin (Ig) E [2]. The Th1 immune response in chronic AD causes lichenification or desquamation [3] and results in an immune response involving interferon (IFN)-γ, interleukin (IL)-1α and -2, and transforming growth factor (TGF)-β [3,4]. Th2-related cytokines, including IL-4, -5, and -13, increase the lesional and nonlesional skin surface area in acute AD [5]. Receptors on the surface of the mast cells bind to IgE and the mast cells can increase IL-6, -1β, and tumor necrosis factor (TNF)-α secretion [7]

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