White Wine Pomace Mitigates Hypoxia in 3D SH-SY5Y Model

Hypoxia-induced reactive oxygen species (ROS) contribute to neuronal death and play a major role in various neurodegenerative diseases. The use of food by-products with antioxidant and anti-inflammatory properties, such as white wine pomace products (wWPPs), could be valuable not only allows for their revalorization but also for their potential in disease prevention. The aim of this study was to evaluate the neuroprotective effect of bioaccessible wWPP against hypoxia in 3D models of the SH-SY5Y human neuroblastoma cell line Cells were treated with 1.5 μg GAE/mL of bioaccessible wWPP and then subjected to hypoxia induced by CoCl2. Cell viability, ROS levels, and gene expression were assessed. Hypoxia significantly increased the expression of the hypoxia-inducible factor gene(HIF1), cell deathand ROS levels, while pretreatment with bioaccessible wWPP mitigated these effects. Hypoxia also altered the mRNA expression of Nrf2, NF-kB, and Nrf2 inhibitor (Keap1), resulting in increased NF-kB and Keap1 expression and decreased Nrf2 levels. Bioaccessible wWPP fractions were able to reverse these changes, restoring mRNA expression to control levels and upregulating antioxidant enzymes like SOD2. These results suggest a potential neuroprotective effect of wine pomace and highlight the relevance of using natural products from the food industry in disease prevention.