Buccato, Daniele Giuseppe (2025) RESEARCH AND DEVELOPMENT OF NEW INGREDIENTS FOR FOOD SUPPLEMENTS. [Tesi di dottorato]

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Abstract

From a regulatory point of view, dietary supplements are foods and are intended to support specific nutritional and physiological functions without claiming to prevent or treat diseases. In this context, a functional ingredient is a defined component, often plant-derived, that shows a reproducible biological effect at feasible doses. Turning a plant extract into a candidate food supplement ingredient requires two steps. First, generation of active substances: compounds are characterized, digested and, when not absorbed in the upper part of gastrointestinal tract, transformed by the colonic microbiota into bioactive metabolites. Second, action on biological targets: molecules able to engage receptors or modulate enzymes in target cells. This thesis presents three independent studies that reflect both routes. As far as gut health is concernet, we studied a pomegranate (P. granatum L.) extract aimed at general intestinal health and a sea buckthorn (H. rhamnoides L.) extract with a functional constipation-oriented rationale, applying in vitro simulated digestion and anaerobic fecal fermentation. Both extracts resulted to modulated microbial fermentation profiles, with increased production of short-chain fatty acids (SCFAs); for H. rhamnoides, Aquaporin-3 (AQP3) expression was significantly modulated in epithelial models. On the ERα-mediated signaling pathway, we evaluated three extracts (A, B and Humulus lupulus L.) with potential phytoestrogenic activities for signals related to menopausal vasomotor symptoms, probing receptor-mediated action in target cells. In MCF-7 cells, the extracts increased progesterone receptor (PgR) expression at non-cytotoxic concentrations. Taken together, our findings provide clear endpoints (SCFAs, AQP3, PgR) and support the progression toward the next research phases of functional ingredients for food-supplement use, that are the evaluation of their activities in human through randomized controlled clinical trials.

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