UVA radiation from the sun is the main external stimulus in the pathogenesis of skin photo-aging. This process is associated with cellular oxidative stress. Here we aim at showing the protective effect of d-Tetramannuronic Acid Tetrasodium Salt (M4), a natural product, against UVA (30J/cm2) irradiation-induced oxidative stress and photo-aging in HaCaT cells, and to reveal the molecular mechanism underlying the protective efficacy. M4 pretreatment significantly increased HaCaT cell viability and MMP, suppressing UVA-induced ROS generation. Moreover, M4 treatment prevented the UVA-induced photo-aging of HaCaT cells (the reduction of cell viability, mitochondria dysfunction, and SIRT1/pGC-1α deregulation). Notably, the anti-photo-aging potential of M4 was directly associated with the increased expression of MMP and SIRT1, which was followed by the up-regulation of pGC-1α, D-LOOP, and Mt-TFA, and the transcriptional activation of NRF1/NRF2. Therefore, M4 is useful for the protection of skin cells from UVA-induced photo-aging.

中文翻译：

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d-四甘露糖醛酸四钠盐对UVA诱导的HaCaT细胞光老化的保护作用。

来自太阳的UVA辐射是皮肤光老化发病机理的主要外部刺激。该过程与细胞氧化应激有关。在这里，我们旨在显示天然产物d-四甘露糖醛酸四钠盐（M4）对HaCaT细胞中UVA（30J / cm2）辐射诱导的氧化应激和光老化的保护作用，并揭示其潜在的分子机制防护功效。M4预处理可显着提高HaCaT细胞的活力和MMP，从而抑制UVA诱导的ROS生成。此外，M4处理阻止了UVA诱导的HaCaT细胞光老化（细胞活力降低，线粒体功能障碍和SIRT1 /pGC-1α失调）。值得注意的是，M4的抗光老化能力与MMP和SIRT1的表达增加直接相关，随后是pGC-1α，D-LOOP和Mt-TFA的上调，以及NRF1 / NRF2的转录激活。因此，M4可用于保护皮肤细胞免受UVA诱导的光老化。