White wine pomace mitigates hypoxia in 3D SH-SY5Y model

Hypoxia-induced reactive oxygen species (ROS) contribute to neuronal death and are a major factor in various neurodegenerative diseases. Currently, there is a need for the development of effective strategies for the control of these diseases. The application of food by-products with antioxidant properties, such as white pomace products (wWPPs), is valuable as it not only allows their revalorization but also shows potential for disease prevention.

The objective of this study was to evaluate the neuroprotective effect of bioaccessible wWPPs against hypoxia in SH-SY5Y human neuroblastoma cell line (ATCC-CRL2266™). Previous research demonstrated a positive effect in 2D in vitro models but did not explore 3D models. As a key innovation in this study, a 3D spheroid model was used, as it more closely mimics in vivo conditions. The 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 evaluated.

Hypoxia significantly increased hypoxia-inducible factor (HIF1) gene expression, cell death, and ROS levels, while the pretreatment with bioaccessible wWPP mitigated these effects. Hypoxia also altered the mRNA expression of nuclear factor-like 2 (Nrf2), nuclear factor κB (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, regulating the mRNA expression to control levels and upregulating antioxidant enzymes like superoxide dismutase 2.

In conclusion, bioaccessible wWPPs showed significant potential in mitigating hypoxia effects in a 3D SH-SY5Y model. 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. However, in vivo studies are necessary to better understand the potential use of these food by-products as functional foods.

The authors thank to MICIU and ERDF (Project PGC2018-097113-B-I00).