<br>Topsentin（一种来自海洋海绵 Spongosorites genitrix 的双（吲哚）生物碱）通过调节 UVB 照射的人角质形成细胞中的 COX-2 和 Mir-4485 表达来发挥光保护活性。,Marine Drugs

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Topsentin（一种来自海洋海绵 Spongosorites genitrix 的双（吲哚）生物碱）通过调节 UVB 照射的人角质形成细胞中的 COX-2 和 Mir-4485 表达来发挥光保护活性。
Marine Drugs ( IF 4.9 ) Pub Date : 2020-01-29 , DOI: 10.3390/md18020087
Jiyoung Hwang ₁ , Donghwa Kim ₁ , Jae Sung Park ₁ , Hyen Joo Park ₁ , Jongheon Shin ₁ , Sang Kook Lee ₁

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皮肤是保护身体免受环境压力的重要屏障。然而，暴露于紫外线辐射（UV）和各种环境氧化应激会导致皮肤炎症。环加氧酶-2 (COX-2) 是一种诱导酶，可介导前列腺素 E2 (PGE2) 的形成，以对抗内部和外部炎症刺激。因此，抑制COX-2是维持皮肤健康、预防皮肤炎症和癌变的重要途径。 Topsentin 是一种从海洋海绵 Spongosorites genitrix 中分离出来的双（吲哚基）咪唑生物碱，据报道具有抗肿瘤和抗微生物活性。然而，topsentin对皮肤炎症的影响及其潜在的分子机制尚未阐明。在本研究中，我们确定了 Topsentin 对 UVB 照射的人表皮角质形成细胞 HaCaT 细胞的光保护作用。 Topsentin 抑制 COX-2 表达及其上游信号通路 AP-1 和 MAPK。此外，topsentin 还能抑制 miR-4485（一种从微阵列中选出的新生物标志物）及其靶基因肿瘤坏死因子 α 诱导蛋白 2 (TNF-α IP2)。 Topsentin 的光保护作用也在重建的人体皮肤模型中得到证实。这些发现表明托普森丁可能作为治疗皮肤炎症介导疾病的化妆品配方的潜在候选者。

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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.

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.

更新日期：2020-03-26

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