New Insights Into the Phytochemical Composition and Biological Potential of Leaf Extracts From Algerian Autochthonous...

Vitis vinifera leaves are abundant by-products of the grape industry, often discarded as agricultural waste. This study explores the in vitro and in silico antioxidant, antidiabetic, and antibacterial properties of hydromethanolic crude extracts from grapevine leaves from five local grapevine varieties in Algeria (Chikki, Azorith-fereinguel, Bezoul El-khadem d'Algérie, Amesski El Hamma, and Hasram). Extracts were prepared via ultrasonic-assisted extraction, with subsequent phytochemical profiling performed by liquid chromatography/mass spectrometry (LC/MS). The analysis revealed 17 identified phenolic compounds, primarily flavanols, and a few phenolic acids, including Isoquercitrin, Hesperidin, and Rutin, which were major compounds. Critically, the Azorith-fereinguel variety exhibited superior antioxidant and antidiabetic activity (IC50: 3.93 μg/mL for DPPH; 43.61 μg/mL for ABTS; 75.12 μg/mL for RP; 22.46 μg/mL for α-amylase; and 25.30 μg/mL for α-glucosidase), outperforming many standard natural extracts and approaching the efficacy of synthetic controls. Furthermore, three varieties (Azorith-fereinguel, Bezoul El-khadem, Amesski El Hamma) showed potent antibacterial activity against four pathogens, with minimum inhibitory concentrations lower than standard antibiotics, indicating a potential solution for antibiotic resistance. In silico analyses revealed that hesperidin and rutin have high binding affinities to key enzyme active sites, providing a mechanistic basis for the observed bioactivity. These findings transform grapevine leaves from agricultural waste into a high-value, multi-functional natural product. This work provides a scientific foundation for developing grapevine leaf extracts into affordable, accessible nutraceuticals, functional food ingredients, or natural food preservatives for managing oxidative stress, diabetes, and bacterial infections, while simultaneously valorizing an abundant agro-industrial by-product within a circular food economy, particularly in resource-limited settings where grape by-products are abundant.