D-Optimal Design-Based Ultrasound-Assisted Extraction Optimization and Extensive Bio-Structural Analysis of Phenolic Compounds from Romanian Cornelian Cherry (Cornus mas L.) Genotypes

Cornelian cherry (Cornus mas L.) fruits are increasingly recognized for their rich phytochemical composition and health-promoting properties, which position them as promising candidates for nutraceutical and functional food applications. This study aimed to optimize ultrasound-assisted extraction (UAE) of phenolic compounds using a D-optimal design and to compare the phenolic profiles and bioactivities of ten Romanian genotypes (B351, F581, F2021, FXI1, M13, M16, MH41, MH51, SB3, and SB23). Optimal UAE conditions, 70% ethanol, 60 min, and 20% amplitude, yielded a TPC of optimized extract of 32.1 mg GAE/g and an antioxidant capacity (ABTS) of 80.2 mg TE/g lyophilized extract. Phytochemical analysis identified 295 phenolic compounds, with the optimized extract containing 1736.2 µg Eq/g dry matter, particularly enriched in flavanols (356.8 µg Eq/g) and other phenolics (853.2 µg Eq/g). Significant genotypic variability was observed: TPC ranged from 9.1 to 23.3 mg GAE/g extract, and antioxidant activities ranged from 20.9 to 47.5 mg TE/g (DPPH), 23.0 to 57.8 mg TE/g (FRAP), and 23.5 to 57.6 mg TE/g (ABTS). Enzyme inhibition assays revealed moderate inhibition of α-glucosidase (IC50: 119.7–329.0 µg/mL), α-amylase (IC50: 162.6–1447.6 µg/mL), and pancreatic lipase (IC50: 1179.1–1824.0 µg/mL). Correlation analysis highlighted cyanidin, catechin, and oleuropein equivalents as key contributors to bioactivity. These results underscore the relevance of genotype selection and process optimization in maximizing the functional potential of C. mas extracts for the prevention of oxidative stress and metabolic disorders.