Abstract
Skin is an important barrier to protect the body from environmental stress. However, exposure to ultraviolet radiation (UV) and various environmental oxidative stresses can cause skin inflammation. Cyclooxygenase-2 (COX-2) is an inducible enzyme that mediates the formation of prostaglandin E2 (PGE2) against internal and external inflammatory stimulations. Therefore, the inhibition of COX-2 is an important approach to maintain skin health and prevent skin inflammation and carcinogenesis. Topsentin, a bis(indolyl)imidazole alkaloid isolated from the marine sponge Spongosorites genitrix, has been reported to exhibit anti-tumor and anti-microbial activities. However, the effect of topsentin on skin inflammation and its underlying molecular mechanism has not been elucidated. In the present study, we identified the photoprotective effects of topsentin on UVB irradiated human epidermal keratinocyte HaCaT cells. Topsentin suppresses COX-2 expression and its upstream signaling pathways, AP-1 and MAPK. Furthermore, topsentin inhibits miR-4485, a new biomarker selected from a microarray, and its target gene tumor necrosis factor alpha induced protein 2 (TNF-α IP2). The photoprotective effect of topsentin was also confirmed in a reconstructed human skin model. These findings suggest that topsentin may serve as a potential candidate for cosmetic formulations with skin inflammatory-mediated disorder.
Highlights
Skin functions as a barrier to protect the body, and it is constantly exposed to chemical and environmental stress [1]
Topsentin significantly inhibited the amount of secreted prostaglandin E2 (PGE2) with an IC50 value of 1.22 μM (Figure 1C)
For evaluation of the cytotoxicity of topsentin, cell viability was measured by MTT assay (Figure 1D); it was found that topsentin did not exhibit significant cytotoxicity
Summary
Skin functions as a barrier to protect the body, and it is constantly exposed to chemical and environmental stress [1]. Prolonged exposure to such stresses causes skin damage and may induce skin cancer [2]. Most UVB is absorbed in the epidermis, the outermost skin layer, and the majority of the epidermis consists of keratinocytes [7] These keratinocytes, which act as a physical barrier, have diverse receptors and can stimulate signal transduction pathways to other layers of the skin [8,9]
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