Simulated Gastrointestinal Digestion Modulates Anticholinesterase, Antioxidant, and Anti-Inflammatory Activities of Vegan Soups Rich in Natural Cholinesterase Inhibitors

Background/Objectives: Dietary strategies targeting oxidative stress, neuroinflammation and cholinergic dysfunction are increasingly investigated as supportive approaches for maintaining cognitive health. Soups constitute a practical functional food matrix due to their compositional complexity and suitability for regular consumption. However, their bioactivity may be substantially altered during digestion. Methods: Previously, we created optimized mushroom, asparagus, leek, and sea buckthorn vegan lunch soups rich in cholinesterase inhibitors. This study evaluated digestion-induced changes in anticholinesterase, antioxidant, and anti-inflammatory activities using a standardized static in vitro digestion model (INFOGEST). Results: Fresh soups contained 90.43–247.36 µg GAE/cm3 of total polyphenols, which significantly decreased during oral–intestinal digestion, followed by stabilization or partial recovery during the colonic phase. Acetylcholinesterase and butyrylcholinesterase inhibitory activities showed soup-specific and digestion stage-dependent patterns, with an overall decline after bacterial incubation. Antioxidant capacity assessed by DPPH•, ABTS•+, and cyclic voltammetry revealed dynamic redox shifts across digestion stages, while endogenous antioxidant enzymes (SOD, CAT, GR, GPx) and COX-2 activity were differentially modulated. Cell-based assays demonstrated low cytotoxicity and moderate, concentration-dependent cytokine modulation. Conclusions: Overall, gastrointestinal digestion and microbial activity markedly reshape the bioactivity of plant-based soups, indicating that the colonic phase is critical for realistic evaluation of functional food potential and supporting digestion-aware assessment of dietary strategies relevant to cognitive and inflammatory health.