Inhibitory effects of Cinnamomum cassia extract on atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice

Abstract

Aim of the study

: Cinnamomum cassia (C. cassia) has been traditionally used to treat allergic disease as well as dyspepsia, gastritis, and blood circulation disturbances. However, the antiallergic properties of C. cassia have not been fully verified using scientific tools. This study investigated the effectiveness of C. cassia extract (CCE) as an antiallergic agent in atopic dermatitis model and underlying mechanism.

Materials and methods

: The effect of CCE on mite antigen-treated NC/Nga mice was evaluated by examining skin symptom severity, levels of serum IgE, tumor necrosis factor-α (TNF-α), and histamine, skin histology, and mRNA expression of cytokines in the skin lesions. Moreover, the effect of CCE on TNF-α-and interferon-γ (IFN-γ)-induced chemokine production in human keratinocytes was investigated using ELISA.

Results

: CCE treatment of NC/Nga mice reduced the dermatitis score and the levels of serum IgE, histamine, and TNF-α. Histological examination showed inhibition of the thickening of the epidermis/dermis and reduced dermal infiltration of inflammatory cells. In skin lesions, mRNA expression of IL-4, TNF-α, and thymus and activation-regulated chemokine (TARC) was inhibited by CCE treatment. The production of TARC, macrophage-derived chemokine, and RANTES from IFN-γ-and TNF-α-stimulated human keratinocytes was suppressed by CCE treatment in a dose-dependent manner.

Conclusions

: CCE inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response.

Introduction

Atopic dermatitis is a chronic inflammatory skin disease with an increasing prevalence in industrialized countries. It commonly presents during early infancy and childhood but also can persist into or start in adulthood (Spergel and Paller, 2003). The major clinical symptoms of atopic dermatitis are pruritic and chronic eczematous skin lesions that are distinguished by infiltration of inflammatory cells consisting of T lymphocytes, monocytes/macrophages, eosinophils, and mast cells (Soter, 1989, Leung and Bieber, 2003). In atopic dermatitis, skin injury due to environmental allergens, scratching, or microbial toxins activates keratinocytes to induce production of proinflammatory cytokines (Leung et al., 2004). Various chemokines and adhesion molecules are induced by these proinflammatory cytokines, leading to the recruitment of pathogenic leukocytes to the skin (Homey et al., 2006). T-helper 2 (Th2)-type T cells, which produce IL-4, IL-5, and IL-10, play major roles in acute atopic dermatitis, and Th1-type cytokines such as interferon-γ (IFN-γ) are involved in chronic atopic dermatitis (Vestergaard et al., 1999, Leung et al., 2004). In most patients with atopic dermatitis, IgE levels in the circulation are elevated, which is attributed to the high production of IL-4, an inducer of IgE production.

The inbred NC/Nga mouse strain was established in 1957 using a Japanese mouse strain (Nishiki–Nezumi). When these mice are placed in conventional surroundings and not maintained under specific pathogen-free (SPF) conditions, clinical signs including scratching behavior appear, and IgE levels are elevated beginning at 8 weeks of age, followed by the onset of eczematous conditions and infiltration of various inflammatory cells into the skin lesions (Matsuda et al., 1997, Vestergaard et al., 1999). Thus, NC/Nga mice are very useful animal models for investigating the pathogenesis of human atopic dermatitis. Patients with atopic dermatitis are highly sensitized to house dust mite allergens. The body and feces of Dermatophagoides farinae, a major species of house dust mites, are well-known major environmental allergens. Previously, it was reported that D. farinae extract (DfE) induces atopic dermatitis-like skin lesions in NC/Nga mice (Matsuoka et al., 2003, Yamamoto et al., 2007).

In general, topical steroid therapy is crucial for the treatment of atopic dermatitis, but it cannot be administrated long term due to its side-effects (Leung and Bieber, 2003). Results from several studies indicate that patients with atopic dermatitis may benefit from oriental herbal medicine therapy (Gao et al., 2005, Kim et al., 2008). Cinnamomum caccia Presl (C. cassia), also known as Chinese cinnamon, is a small evergreen tree belonging to the family Lauraceae. C. cassia bark or cortex is a natural spice and herb commonly used in traditional medicine to treat dyspepsia, gastritis, blood circulation disturbances, and allergic disease (Leung and Foster, 1996, Nagai, 2004). C. cassia has been shown to have many pharmacological properties, such as antiulcerogenic (Akira et al., 1986), antiinflammatory (Atta and Alkofahi, 1998), antipyretic (Kurokawa et al., 1998), antimicrobial (Lee and Ahn, 1998), and antidiabetic activity (Dugoua et al., 2007). It has been also reported that an aqueous extract of C. cassia inhibited Arthus allergic reaction in rabbits (Nagai et al., 1982). Novel diterpenes were isolated from bark of C. cassia and identified as the active antiallergic substances (Nohara et al., 1982, Nohara et al., 1985). Despite traditional usage of C. cassia to treat allergic disease, its mechanism has not been fully verified using scientific tools.

Under the circumstances, we investigated the antiallergic effects of C. cassia extract on NC/Nga mice as a model of mite antigen-induced atopic dermatitis. We also determined the effect of C. cassia on chemokine production in the human keratinocyte cell line HaCaT to examine a possible mechanism for the antiallergic effect of C. cassia.