Photoprotective Activity of Topsentin, A Bis(Indole) Alkaloid from the Marine Sponge Spongosorites genitrix, by Regulation of COX-2 and Mir-4485 Expression in UVB-Irradiated Human Keratinocyte Cells

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.

Photoprotection and Skin Pigmentation: Melanin-Related Molecules and Some Other New Agents Obtained from Natural Sources

“…For instance, topsentin which is an alkaloid isolated from the marine sponge Spongosorites genitrix exhibits anti-inflammatory activity in UVB-irradiated human epidermal HaCaT keratinocytes. The photoprotective effect of topsentin was confirmed in a reconstructed human skin model [86]. Topsentin suppresses the expressions of two key targets for the prevention and treatment of skin damage and inflammation after sun exposure, COX-2 and miR-4485.…”

From Sea to Skin: Is There a Future for Natural Photoprotectants?

“…Melanin-related compounds, such as eumelanin from sepia ink, have been proposed as natural UV filters and antioxidants, although their actual use in topical formulations is limited by the unaesthetic dark color conferred to the skin by any product containing eumelanin [ 140 ]. Another compound whose photoprotective abilities have recently been investigated is topsentin, a bis(indolyl)imidazole alkaloid, isolated from the marine sponge Spongosorites genitrix [ 141 ]. It has been shown to inhibit the expression of cyclooxygenase-2, an important enzyme involved in prostaglandin E2 (PGE2) synthesis, and miR-4485, a newly identified inflammation marker in UVB-irradiated human keratinocytes, and lowered PGE2 formation in a reconstructed human skin model [ 141 ].…”

“…Another compound whose photoprotective abilities have recently been investigated is topsentin, a bis(indolyl)imidazole alkaloid, isolated from the marine sponge Spongosorites genitrix [ 141 ]. It has been shown to inhibit the expression of cyclooxygenase-2, an important enzyme involved in prostaglandin E2 (PGE2) synthesis, and miR-4485, a newly identified inflammation marker in UVB-irradiated human keratinocytes, and lowered PGE2 formation in a reconstructed human skin model [ 141 ].…”

Bioactive Bis(indole) Alkaloids from a Spongosorites sp. Sponge

“…Among the numerous sponge-derived alkaloids, topsentins are one of the most well-known classes; thus, extensive research has been conducted with respect to their structural determination, total synthesis, and bioactivity [ 15 , 16 , 17 ]. The diverse types of bioactivity reported include anti-inflammatory, anti-bacterial, anti-cancer, DNA-intercalating, and skin photoprotective, as well as the inhibition of Gram-positive bacterial enzyme sortase A, from our previous study [ 17 , 18 , 19 , 20 , 21 ]. These bis(indole) alkaloids, typically bearing an imidazole ring as the central core, were originally isolated from the sponge Spongosorites genitrix , which belongs to the family Halichondriidae [ 21 , 22 ].…”

“…The diverse types of bioactivity reported include anti-inflammatory, anti-bacterial, anti-cancer, DNA-intercalating, and skin photoprotective, as well as the inhibition of Gram-positive bacterial enzyme sortase A, from our previous study [ 17 , 18 , 19 , 20 , 21 ]. These bis(indole) alkaloids, typically bearing an imidazole ring as the central core, were originally isolated from the sponge Spongosorites genitrix , which belongs to the family Halichondriidae [ 21 , 22 ]. Experiencing wide structural variations at both the imidazole moiety and the indole functionality, the succeeding analogs of topsentins include dragmacidins, hamacanthins, hytinadine A, nortopsentins, and rhopaladins from the genus Spongosorites and even a Rhopalaea sp.…”