Functional properties of fructans and their potential role in management of intestinal inflammatory pathologies

Transcription

1 Functional properties of fructans and their potential role in management of intestinal inflammatory pathologies Dr.ssa Valentina Pasqualetti Unità di Ricerca di Scienze degli Alimenti e della Nutrizione Facoltà Dipartimentale di Medicina e Chirurgia

2 PLoS ONE 9(5): e9803; doi: /journal.pone Research Unit of Food and Nutrition Sciences Laboratory of Plant Biochemistry and Food Sciences (Centro Integrato di Ricerca) Unit of Gastroenterology (Policlinico Universitario)

3 Inulin Poaceae Liliaceae Asteraceae or Compositae Fructose linear polymer, β(2-1) glycosidic bonds, DP of (variable according to plant source, time of plant life cycle, processing conditions ). Mainly present in dicotyledon plants, especially Asteraceae or Compositae. Food industry: natural emulsifier and stabilizer; sugar and fat replacement. Pharmacology: carrier in «drug delivery» (hydrogels); adjuvant agent in vaccine formulation; possible excipient in pharmaceutical formulations.

4 Fructans: «Pro-healthy» effects Soluble dietary fibers which stimulate GI functions. Modulation of growth, composition and functionality of the microbiota (prebiotic and bifidogenic effect). Increase of mineral absorption (Ca 2+ and Mg 2+ ). Improvement of lipid metabolism. Regulation of endocrine gastrointestinal activities (appetite) by modulating the hormone balance. Regulation of immunoregulatory activitiy contributing to the body's defense. Reduction of colon cancer risk.

5 Fructans: TEAC reactivity (scavenging vs ABTS + ) ASC = nmol TE/mg GSH = nmol TE/mg p < 0.05 (ANOVA test) (3 DP 30) (DP 125) Total antiox capability of FOS is an typical attribute of this class of molecules that is determined by the overall structural characteristics of the polymer and not by its constituent units. They have a lower antiox power than ASC and GSH, however, unlike them, they pass along the whole GI tract without being absorbed and, therefore, they have positive action in colon, that is not reached by other antioxidant molecules which are absorbed in the first part of human gut.

6 In vitro simulation of the human digestive process Total antiox capability of Inulin pre- and post-digestion INU p = ns (ANOVA test) Total antiox capability of Ascorbate pre- and post-digestion ASC p < (ANOVA test) This supports the use of fructans in human nutrition as antioxidant molecules being able to reach the intestine (colon), maintaining unchanged their antioxidant properties.

7 Ex vivo experiments on human colon mucosa Ex vivo experimental model AIM: to test the real protective effects of INU in vivo, directly on the intestinal tissue subjected to pro-oxidant and pro-inflammatory stimulus (exposure to LPS from pathogenic strain of E. coli serotype 0111:B4)

8 TEAC reactivity and fructose quantification of supernatant and undernatant liquids Total antiox capability of supernatant and undernatant liquids p < (ANOVA test) Confirmed stability of INU to intestinal environment. Inability of INU to cross the intestinal mucosa (absence of translocations). No damage to the tissue during the preparation of the model that remains intact. INU plays a protective (antiox) effect directly to the site of inflammatory pathology by counteracting ox stress (ROS) in situ associated with the inflammatory process.

9 Oxidative damage to mucosal proteins L esposizione a LPS induce un danno ox alle cellule. Il trattamento con b INU è in grado di proteggere la mucosa intestinale contrastando e prevenendo a l ox irreversibile delle proteine mucosali. a Exposure to LPS induces an ox damage to the mucosal cells. Treatment with INU is able to protect the intestinal mucosa by counteracting and preventing the irreversible ox of mucosal proteins. p < 0.01 (ANOVA test)

10 p < 0.05 (Student t s test) Analysis of the motility of the SMCs a a a No morphological damage and significant change in the length of colon SMCs (Smooth Muscle Cells) compared to the control cells. a Resting Cell Length = 141,7 µm b a Exposure (30') to LPS-undernatant causes a reduction in the Ach-induced maximal contraction compared to the contraction induced in cells incubated with N-undernatant (damage contrasted and prevented by treatment with LPS+INU-undernatant).

11 Conclusions INULIN proven prebiotic and bifidogenic effect; extensive industrial use, security and lack of noticeable side effects; anti-inflammatory and antioxidant action; protective effect against intestinal motility impairment. Possible use of INU as ingredient with ROS scavenger action in the formulation of functional foods naturally enriched or fortified with it. Possible use of INU for the realization of new therapeutic opportunities as a potential clinical approach and medical strategy supporting the conventional anti-inflammatory drug treatment for the prevention of human IBD (Inflammatory Bowel Diseases) and IBS (Irritable Bowel Syndrome).

12 Acknowledgments Research Unit of Food and Nutrition Sciences Laboratory of Plant Biochemistry and Food Sciences (Centro Integrato di Ricerca Università Campus Bio-medico di Roma) Prof.ssa Laura De Gara Dr.ssa Vittoria Locato Unit of Gastroenterology (Policlinico Universitario Campus Bio-medico di Roma) Prof. Michele Cicala Prof.ssa Rossana Alloni Dr.ssa Annamaria Altomare Dr. Michele Pier Luca Guarino