Subcritical Water Extract from Grape Pomace Protects Human Bronchial Epithelium Cells by Mitigating Oxidative Stress Through Nrf2 Pathway

In the context of the circular economy, the valorization of natural biomolecules from by-products has recently represented a major goal in health promotion. From this perspective, this study examined the antioxidant potential of Sicilian white grape pomace from the Pinot Gris variety, using subcritical water extraction as an eco-friendly and innovative method to recover bioactive compounds. Different extraction parameters allowed for comparing the potential of various fractions. Among these, the Subcritical Water Extract obtained after 5 min at 160 °C (SWE160.1) was rich in gallic acid and protocatechuic acid, as evidenced by characterization with UHPLC-Q Exactive Orbitrap-HRMS system. SWE160.1 showed efficacious antioxidant activity, as confirmed by DPPH assay and total polyphenol and flavonoid content. Interestingly, SWE160.1 displayed cytotoxic activity in tumor cell lines, while preserving the viability of non-tumor bronchial epithelial cells. Specifically, SWE160.1 protected these cells from exogenous oxidative stress, reducing the ROS levels and activating Nrf2-mediated antioxidant response. Surprisingly, upregulation of antioxidant enzymes (HO-1 and SOD-2) induced by SWE160.1 was maintained in the presence of lipopolysaccharide, indicating a specific involvement of SWE160.1 in the anti-inflammatory response. Finally, SWE160.1 was also able to limit the formation of stress granules following acute stress, thereby supporting its potential to maintain cellular homeostasis. Overall, this study highlights the potential of grape pomace as a source of active molecules to prevent oxidative stress and inflammation.