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/cm) 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.
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