Comparative assessment of cornelian cherry fruits and extract during simulated gastrointestinal digestion: phytochemistry, biological activities, and in silico evaluation

Bioactive compounds from Cornus mas L. are commonly studied as extracts, leaving unclear whether whole fruit and a corresponding extract behave differently during digestion. Ground cornelian cherry fruit (CMF) and an optimized ultrasound-assisted extract (CME) underwent standardized static in vitro gastrointestinal digestion (INFOGEST 2.0), with results normalized to fresh-fruit equivalents (FFE). Soluble fractions were analyzed for total phenolic and anthocyanin contents, antioxidant activity, and phytochemical profiles by HPLC-DAD-ESI-MS, while principal component analysis and hierarchical clustering were implemented to characterize phytochemical variation. Intestinal digesta were evaluated for minimum inhibitory concentration (MIC) and effects on Caco-2 and HT-29 cell viability. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction and molecular docking were implemented to provide potential exploratory mechanisms for observed effects. After intestinal digestion, total phenolics reached 4.18 and 1.63 mg GAE/g FFE in CMF and CME, respectively. The sum of semi-quantified bioactive compounds reached 4062.61 and 1872.11 μg/g FFE, respectively, corresponding to a 2.17-fold higher FFE-normalized content in intestinal CMF digesta. Intestinal-to-oral soluble recovery (IOSR) of anthocyanins was 311.9% for CMF and 32.8% for CME. CMF retained higher antioxidant activity and lower FFE-normalized MICs, although antimicrobial activity was limited. On an FFE-normalized basis, intestinal CMF digesta were 3.25- and 2.61-fold more active than intestinal CME digesta against Caco-2 and HT-29 cells, although per mass of digesta the IC 50 values were similar (Caco-2) or nearly identical (HT-29). The predicted intestinal absorption was low (1.7–10.6%), with sweroside showing the strongest caspase-3 docking affinity (−8.0 kcal/mol). Overall, under the tested preparation-specific loading conditions, CMF showed higher FFE-normalized intestinal soluble phytochemical content and retained in vitro activity than CME.