Ramalin Isolated from Ramalina Terebrata Attenuates Atopic Dermatitis‐like Skin Lesions in Balb/c Mice and Cutaneous Immune Responses in Keratinocytes and Mast Cells

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease that involves eczematous skin lesions with pruritic erythematous papules. In this study, we investigated the mitigating effects of ramalin, a component of the Antarctic lichen Ramalina terebrata against AD in vivo and in vitro. Oral administration of ramalin lessened scratching behaviors and significantly reduced both serum immunoglobulin E and IL-4 levels, and mRNA levels of IL-4 and IL-10 in AD-induced Balb/c mice. In vitro, treatment with ramalin produced significantly less inflammatory chemokines and cytokines, including TARC, MCP-1, RANTES, and IL-8 in TNF-α-stimulated HaCaT cells. In addition, ramalin inhibited the activation of nuclear factor-kappa B as well as the phosphorylation of mitogen-activated protein kinases (MAPK). Furthermore, ramalin treatment resulted in decreased production of β-hexosaminidase and proinflammatory cytokines IL-4, IL-6, and TNF-α in 2,4 dinitrophenyl-human serum albumin-stimulated RBL-2H3 cells through blocking MAPK signaling pathways. The results suggest that ramalin modulates the production of immune mediators by inhibiting the nuclear factor-kappa B and MAPK signaling pathways. Taken together, ramalin effectively attenuated the development of AD and promoted the mitigating effects on Th2 cell-mediated immune responses and the production of inflammatory mediators in mast cells and keratinocytes. Thus, ramalin may be a potential therapeutic agent for AD. Copyright © 2016 John Wiley & Sons, Ltd.

Artemisia anomala Herba Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and the Production of Pro-Inflammatory Mediators in Tumor Necrosis Factor Alpha-/Interferon Gamma-Induced HaCaT Cells

“…In this experiment, we elucidated that EAA inhibits the production of pro-inflammatory cytokines and chemokines in TNF-α/IFN-γ-stimulated keratinocytes. In this experiment, we elucidated that EAA inhibits the production of pro-inflammatory cytokines and chemokines, such as IL-6, IL-8, RANTES, and TARC in TNF-α/IFN-γ-stimulated keratinocytes, consistent with previously reports [ 17 , 18 ].…”

“…Keratinocytes are located in the outermost part of the epidermis of the skin and play an important role in the pathogenesis of inflammatory skin disease, in addition to secreting pro-inflammatory mediators as a cellular source of risk signals. Activated keratinocytes can induce the upregulation of pro-inflammatory chemokines and chemokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), regulated upon activation (RANTES; CCL5), and TARC; CCL17) [ 17 ]. These skin-related cytokines and chemokines are involved in the exacerbation of AD by selectively controlling the migration of immune cells to the skin lesion site and stimulating an inflammatory response [ 18 ].…”

Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model

“…Mast cell activation mediated by IgE leads to a release of various chemical mediators which results in infiltration of inflammatory cells such as eosinophils and lymphocytes into the skin lesion [4]. CD4 + T cells and mast cells in the skin lesions are also involved in the pathogenesis of AD [5,6,7,8]. It has been reported that 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesion mouse model showed increased serum IgE and Th2 cytokines such as IL-4, IL-5, and IL-13 [9,10].…”

Anticancer Activity of Ramalin, a Secondary Metabolite from the Antarctic Lichen Ramalina terebrata, against Colorectal Cancer Cells

“…Although previous studies have revealed many biological effects of ramalin, such as antioxidant activity and anticancer activity [ 17 , 18 , 19 ], the wound-healing effects of ramalin on cancer cells have not yet been reported. The wound-healing effects of ramalin at the concentrations that induced no cytotoxicity (12.5 and 25 μg/mL) were evaluated in HCT116 cells by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) cell viability assay ( Figure 2 A).…”

“…More than 1000 metabolites have been identified as lichen-derived compounds, and these compounds have a wide range of biological activities such as anti-inflammatory, antioxidant, cytotoxic, and antiproliferative activities [ 16 ]. Recent studies have shown that ramalin, a secondary metabolite derived from the Antarctic lichen Ramalina terebrata ( Figure 1 ), has significant antioxidant and anti-inflammatory activities [ 17 , 18 ]. However, the biological activity of ramalin in carcinogenesis and cancer therapy has not been well investigated.…”