Improved Anti-Inflammatory Effects of Liposomal Astaxanthin on a Phthalic Anhydride-Induced Atopic Dermatitis Model.

Yong Sun Lee,Min Jong Song,Seong Hee Jeon,Hyeon Joo Ham,Jin Tae Hong,Hee Pom Lee

doi:10.3389/fimmu.2020.565285

Abstract

Previously, we found that astaxanthin (AST) elicited an anti-inflammatory response in an experimental atopic dermatitis (AD) model. However, the use of AST was limited because of low bioavailability and solubility. We hypothesized that liposome formulation of AST could improve this. In this study, we compared the anti-inflammatory and anti-dermatotic effects of liposomal AST (L-AST) and free AST. We evaluated the effect of L-AST on a phthalic anhydride (PA)-induced animal model of AD by analyzing morphological and histopathological changes. We measured the mRNA levels of AD-related cytokines in skin tissue and immunoglobulin E concentrations in the serum. Oxidative stress and transcriptional activities of signal transducer and activator of transcription 3 (STAT3) and nuclear factor (NF)-κB were analyzed via western blotting and enzyme-linked immunosorbent assay. PA-induced dermatitis severity, epidermal thickening, and infiltration of mast cells in skin tissues were ameliorated by L-AST treatment. L-AST suppressed AD-related inflammatory mediators and the inflammation markers, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in PA-induced skin conditions. Oxidative stress and expression of antioxidant proteins, glutathione peroxidase-1 (GPx-1) and heme oxygenase-1 (HO-1), were recovered by L-AST treatment in skin tissues from PA-induced mice. L-AST treatment reduced transcriptional activity of STAT3 and NF-κB in PA-induced skin tissues. Our results indicate that L-AST could be more effective than free AST for AD therapy.

Highlights

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by mass release of cytokines [1]
A clinical study indicated that the levels of various antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH), were substantially decreased in patients with AD compared to healthy controls [9]
Western blot analysis showed that the reduction in the expression of the inflammation markers COX-2 and inducible nitric oxide synthase (iNOS) was more pronounced in liposomal AST (L-AST) treated mice when compared to AST treated mice (Figure 1E)

Summary

Introduction

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by mass release of cytokines [1]. Mast cells contribute to AD development and IgE leads to the activation of mast cells through the release of cytokines into skin lesions [5]. The skin is the largest organ of the human body, protecting it from harmful environmental factors, such as chemicals, biologic materials, and allergens. These external materials are known to cause oxidative stress by inducing the generation of reactive species in keratinocytes [6]. A previous study showed that TSLP, which is a trigger factor for the pathogenesis of AD, was increased by reactive oxygen species (ROS) in AD tissues [8]. Increased oxidative stress could contribute to the development of AD

Methods

Results

Conclusion