Inhibitory Effects of Grape Stem Extracts From Douro Varieties on Skin‐Aging Enzymes: A Sustainable Source of Cosmeceutical Agents

Background Grape stems are a major by‐product of the winemaking process and remain largely underexploited despite their richness in bioactive phenolic compounds, representing an opportunity for sustainable valorization within a circular economy framework. Aims This study aimed to characterize the phenolic composition and evaluate the antioxidant and enzyme inhibitory activities of grape stem extracts from different cultivars grown in the Douro Demarcated Region. Methods Grape stems from 12 Vitis vinifera cultivars were extracted and analyzed for total phenolic content, ortho‐diphenols, and flavonoids. Antioxidant capacity was assessed using FRAP and DPPH assays, while bioactivity was further evaluated through elastase and hyaluronidase inhibition assays. Results Total phenolic content ranged from 35.2 to 89.6 mg GAE/g DW, with Sousão exhibiting the highest values. Ortho‐diphenols and flavonoids showed marked cultivar‐dependent variability, with Verdelho and Cercial presenting values above 20 mg CAE/g DW and 15 mg QE/g DW, respectively. Antioxidant activity reached up to 920 μmol TE/g DW (FRAP) and 85% DPPH radical scavenging. Enzyme inhibition assays revealed strong cultivar‐dependent bioactivity, with Sousão, Verdelho, and Gouveio extracts achieving over 60% inhibition of elastase and hyaluronidase. Conclusions The results highlight the significant influence of grape cultivar on the bioactive potential of grape stems and support their valorization as promising raw materials for nutraceutical and cosmeceutical applications.