The protective effect of hesperetin on UVA-induced matrix metalloproteinase-1 (MMP-1) in primary human dermal fibroblasts and mouse skin through modulation of nuclear factor erythroid 2- related factor 2 (NRF2)-regulated antioxidant defenses

Skin aging is an accumulation of collagen degradation caused by matrix metalloproteinase-1 (MMP-1) mainly present in human dermal fibroblasts (HDFs). Increased activity of Nrf2, the transcription factor of antioxidant genes, to counteract oxidative stress is suggested to delay aging process and thus compounds targeting Nrf2 might represent a promising strategy for skin photoprotection. In addition, natural products containing hesperetin were reported to provide photoprotective effects on UVA-induced MMP-1 in HDFs. Aims This study aims to investigate anti-photoaging effects of hesperetin on UVA-mediated MMP-1 induction and collagen depletion through activation of Nrf2-mediated antioxidant defenses (GCLC and NQO-1) in HDFs and the skin of BALB/c mice. Results This study revealed that hesperetin (up to 15 µM) could reduce MMP-1 activity and increase collagen levels in UVA (8 J/cm2)-irradiated HDFs. In vivo immunofluorescence staining showed that treatment with hesperetin (up to 60 µM/cm2) protected against UVA (60 J/cm2)-mediated MMP-1 induction and collagen reduction in association with increase in Nrf2 nuclear localization and its target proteins (GCLC and NQO-1) in mouse skin. In summary, hesperetin exerted anti-photoaging effects on UVA-induced MMP-1 induction possibly through activation of Nrf2-regulated antioxidant defenses in HDFs and mouse skin.