title: A low dose of fermented soy germ alleviates gut barrier injury, hyperalgesia and faecal protease activity in a rat model of inflammatory bowel disease.
abstract: Pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF), IL-1β and TNF-α predominate in inflammatory bowel diseases (IBD) and TNBS colitis. Increased levels of serine proteases activating protease-activated receptor 2 (PAR-2) are found in the lumen and colonic tissue of IBD patients. PAR-2 activity and pro-inflammatory cytokines impair epithelial barrier, facilitating the uptake of luminal aggressors that perpetuate inflammation and visceral pain. Soy extracts contain phytoestrogens (isoflavones) and serine protease inhibitors namely Bowman-Birk Inhibitors (BBI). Since estrogens exhibit anti-inflammatory and epithelial barrier enhancing properties, and that a BBI concentrate improves ulcerative colitis, we aimed to evaluate if a fermented soy germ extract (FSG) with standardized isoflavone profile and stable BBI content exert cumulative or synergistic protection based on protease inhibition and estrogen receptor (ER)-ligand activity in colitic rats. Female rats received orally for 15 d either vehicle or FSG with or without an ER antagonist ICI 182.780 before TNBS intracolonic instillation. Macroscopic and microscopic damages, myeloperoxidase activity, cytokine levels, intestinal paracellular permeability, visceral sensitivity, faecal proteolytic activity and PAR-2 expression were assessed 24 h, 3 d and 5 d post-TNBS. FSG treatment improved the severity of colitis, by decreasing the TNBS-induced rise in gut permeability, visceral sensitivity, faecal proteolytic activity and PAR-2 expression at all post-TNBS points. All FSG effects were reversed by the ICI 182.780 except the decrease in faecal proteolytic activity and PAR-2 expression. In conclusion, the anti-inflammatory properties of FSG treatment result from two distinct but synergic pathways i.e an ER-ligand and a PAR-2 mediated pathway, providing rationale for potential use as adjuvant therapy in IBD.
authors.affiliation: Neuro-Gastroenterology and Nutrition, Institut National de la Recherche Agronomique, UMR1331 Toxalim, INRA/INPT/UPS, Toulouse, France.
authors.forename: Lara
authors.initials: L
authors.lastname: Moussa
authors.forename: Valérie
authors.initials: V
authors.lastname: Bézirard
authors.forename: Christel
authors.initials: C
authors.lastname: Salvador-Cartier
authors.forename: Valérie
authors.initials: V
authors.lastname: Bacquié
authors.forename: Corinne
authors.initials: C
authors.lastname: Lencina
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lévêque
authors.forename: Viorica
authors.initials: V
authors.lastname: Braniste
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ménard
authors.forename: Vassilia
authors.initials: V
authors.lastname: Théodorou
authors.forename: Eric
authors.initials: E
authors.lastname: Houdeau
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005243:Feces / Q000201:enzymology*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000628:therapy; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D044464:Receptor, PAR-2 / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry*; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D015431:Weight Loss / Q000187:drug effects
chemical_list: D016207:Cytokines; D010936:Plant Extracts; D044464:Receptor, PAR-2; D014302:Trinitrobenzenesulfonic Acid; D010447:Peptide Hydrolases