Microbiology Division, CSIR-CLRI, Adyar, Chennai 600020, India.
Photochem Photobiol Sci. 2018 Sep 12;17(9):1229-1238. doi: 10.1039/c8pp00221e.
The present study explores the UVB-induced oxidative stress protective efficacy of the pigmented fungal metabolite (identified as DHICA: 5,6-dihydroxyindole-2-carboxylic acid - a melanin precursor) using human dermal fibroblast (HDF) cells. DHICA is a water soluble pigment of the marine Aspergillus nidulans strain SG 28. Preliminary compatibility studies revealed 95% HDF cell viability with 600 μM concentration of DHICA. HDF cells were exposed to UVB irradiation with and without DHICA pre-treatment and the morphological, physiological and molecular level changes were observed accordingly. The results suggested that UVB exposure increases reactive oxygen species (ROS) generation and subsequent DNA damage in HDF cells, whereas DHICA pre-treatment appreciably reduces ROS generation and DNA damage. DHICA pre-treatment upregulates the antioxidant enzyme expressions and reduces the number of cells in the sub-Go/G1 phase. Gene expression analysis of TNF-α, IL-6, COX-2, NF-κB, Bax and Caspase 3 suggested that pre-treatment with DHICA downregulates the above-mentioned genes and simultaneously upregulates Bcl2 expression. In vivo experiments with BALB/c mice suggested that the topical application of DHICA protected mice skin from UVB-induced oxidative stress (which increases the epidermal thickness as evidenced in the skin sectioning). Thus, DHICA application protects the cells from UVB induced oxidative stress and may find applications in sunscreen cosmetic preparations.
本研究探讨了色素真菌代谢产物(鉴定为 DHICA:5,6-二羟基吲哚-2-羧酸 - 一种黑色素前体)对 UVB 诱导的氧化应激的保护作用,使用人真皮成纤维细胞(HDF)。DHICA 是海洋 Aspergillus nidulans SG 28 菌株的水溶性色素。初步相容性研究显示,DHICA 浓度为 600 μM 时,HDF 细胞的存活率为 95%。将 HDF 细胞暴露于 UVB 辐射下,并进行 DHICA 预处理,观察相应的形态、生理和分子水平的变化。结果表明,UVB 暴露会增加 HDF 细胞中活性氧(ROS)的产生和随后的 DNA 损伤,而 DHICA 预处理可显著减少 ROS 的产生和 DNA 损伤。DHICA 预处理上调抗氧化酶的表达,并减少处于亚 G0/G1 期的细胞数量。TNF-α、IL-6、COX-2、NF-κB、Bax 和 Caspase 3 的基因表达分析表明,DHICA 预处理可下调上述基因,并同时上调 Bcl2 的表达。BALB/c 小鼠的体内实验表明,DHICA 的局部应用可保护小鼠皮肤免受 UVB 诱导的氧化应激(如皮肤切片所示,增加表皮厚度)。因此,DHICA 的应用可保护细胞免受 UVB 诱导的氧化应激,可能在防晒化妆品制剂中得到应用。