Green Extraction and Circular Valorisation of Grape Pomace: A Sustainable Source of Bioactive Compounds with antioxidant potential for Nutraceutical Applications

In recent years, growing attention has been given to sustainable strategies for recovering bioactive compounds from agro-industrial byproducts in line with circular economy principles. This study focuses on valorising grape pomace using subcritical water extraction, an ecofriendly method that uses only water, reducing hazardous solvents and improving resource efficiency. The optimization of extraction parameters enabled the production of fractions with distinct chemical profiles, among which SWE160.1, the extract obtained at the highest temperature used (160 °C) during the first 5 minutes of extraction, was particularly enriched in high-value phenolic compounds. SWE160.1 exhibited a selective cytotoxic activity on different cancer cell lines while preserving the viability of non-tumor human bronchial epithelial cells. In detail, the extract showed significant antioxidant potential in these cells, as demonstrated by its ability to counteract ROS generation, even under oxidative stress conditions, and to promote activation of the Nrf2/HO-1 axis. SWE160.1 maintained the upregulation of antioxidant enzymes even in the presence of LPS, supporting a specific role also in the anti-inflammatory response. Moreover, SWE160.1 counteracted stress granule formation following acute stress, reducing the possibility of converting these transient cytoplasmic granules into toxic aggregates. The dual activity, which combines anticancer potential with protective effects on healthy cells, supports its promising application as a source of health-promoting compounds for the development of innovative nutraceutical formulations. Overall, this study supports a sustainable model in which green extraction technologies enable the transformation of agroindustrial residues into high-value products.