From winery waste to functional foods: therapeutic and nutraceutical potential of bioactive phytochemicals from Vitis vinifera seed byproducts

Vitis vinifera seed byproducts, including grape seed extract (GSE), grape seed oil (GSO), grape pomace (GP), grape seed proanthocyanin extract (GSPE) and grape seed and skin extract (GSSE), represent underutilized yet rich sources of bioactive phytochemicals such as polyphenols, flavonoids and proanthocyanidins. These compounds exert diverse pharmacological effects through modulation of key molecular pathways, including attenuation of oxidative stress, inhibition of pro-inflammatory signaling pathways and regulation of metabolic enzymes. This review systematically aims to consolidate and critically evaluates the phytochemical composition, mechanistic insights and therapeutic potential of Vitis vinifera seed byproducts in human health. A comprehensive literature search following PRISMA guidelines identified 124 relevant studies from databases such as Scopus, ScienceDirect, Web of Science and Google Scholar. Evidence from in vitro, in vivo and clinical studies demonstrates that these bioactive compounds modulate signaling pathways such as NF-kB, PI3K/Akt and AMPK, thereby contributing to antioxidant, anti-inflammatory, cardiometabolic, neuroprotective and antimicrobial effects. Among these byproducts, GSE is the most extensively studied and shows significant efficacy in improving oxidative stress, endothelial function and metabolic parameters. GSPE demonstrates strong cardiometabolic and neuroprotective effects, whereas GP, GSO and GSSE exhibit promising but comparatively underexplored therapeutic potential. Despite preclinical evidence, clinical validation remains limited due to variability in phytochemical composition, dosage and study design. Increasing the bioavailability and standardization of these compounds is necessary for a successful translation to application in functional food and nutraceuticals. Overall, Vitis vinifera seed byproducts represent a sustainable and valuable source of bioactive phytochemicals with significant potential in the prevention and management of non-communicable diseases. Future research should focus on mechanistic validation and well-designed clinical trials to support their clinical application in human health.