Grape Pomace as a Platform for Secondary Metabolite Recovery: Mechanistic Insights into Bioactivity, Processing, and...

The growing interest in plant-derived bioactive secondary metabolites has renewed attention to grape pomace as a promising source within the context of sustainable and circular bioeconomy strategies. Its chemically diverse composition, influenced by cultivar, climate, and processing conditions, has shown a wide range of biological activities, including antioxidative, anti-inflammatory, antimicrobial, antidiabetic, and anticancer effects. Several reviews have addressed its composition, bioactivity, extraction, and applications, but a more integrated understanding of the molecular mechanisms is still needed. This review synthesizes recent evidence on the mechanistic actions of grape pomace metabolites, highlighting their involvement in key pathways such as Nrf2-mediated antioxidant defense, NF-κB-regulated inflammation, AMPK/SIRT1-dependent metabolic regulation, apoptosis-related signaling, and microbiota-driven phenolic metabolism. It also discusses challenges related to raw material variability, process standardization, and industrial scalability, and explores how advances in chemometrics, omics technologies, and data-driven optimization can support future development. Therefore, it provides an integrated perspective linking mechanistic insights with technological considerations to advance the sustainable valorization of grape pomace.