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.