title: Bacteria-Derived Compatible Solutes Ectoine and 5α-Hydroxyectoine Act as Intestinal Barrier Stabilizers to Ameliorate Experimental Inflammatory Bowel Disease.
abstract: Earlier studies showed that the compatible solute ectoine (1) given prophylactically before induction of colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats prevented histological changes induced in the colon and the associated rise in inflammatory mediators. This study was therefore conducted to investigate whether ectoine (1) and its 5α-hydroxy derivative (2) would also be effective in treating an already established condition. Two days after inducing colitis in rats by instilling TNBS/alcohol in the colon, animals were treated orally once daily for 1 week with either 1 or 2 (50, 100, 300 mg/kg). Twenty-four hours after the last drug administration rats were sacrificed. Ulcerative lesions and colon mass indices were reduced by 1 and 2 in a bell-shaped manner. Best results were obtained with 100 mg/kg ectoine (1) and 50 mg/kg 5α-hydroxyectoine (2). The solutes normalized the rise in myeloperoxidase, TNFα, and IL-1β induced by TNBS but did not affect levels of reduced glutathione or ICAM-1, while reducing the level of fecal calprotectin, an established marker for inflammatory bowel disease. The findings indicate that the naturally occurring compatible solutes ectoine (1) and 5α-hydroxyectoine (2) possess an optimum concentration that affords maximal intestinal barrier stabilization and could therefore prove useful for better management of human inflammatory bowel disease.
authors.affiliation: †Scientific Department, Steigerwald Arzneimittelwerk GmbH, Havelstraße 5, Darmstadt, Germany.|⊥Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Heba
authors.initials: H
authors.lastname: Abdel-Aziz
authors.affiliation: ‡Department of Pharmacology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, Egypt.
authors.forename: Walaa
authors.initials: W
authors.lastname: Wadie
authors.affiliation: §Research and Development, Bitop AG, Stockumer Straße 28, Witten, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Scherner
authors.affiliation: ⊥Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: ‡Department of Pharmacology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, Egypt.
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Khayyal
mesh_terms: D000599:Amino Acids, Diamino / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D001419:Bacteria; D003092:Colitis / Q000139:chemically induced; D003106:Colon / Q000187:drug effects; D004534:Egypt; D005978:Glutathione / Q000032:analysis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1; D053583:Interleukin-1beta / Q000494:pharmacology; D007422:Intestines / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D009195:Peroxidase / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000599:Amino Acids, Diamino; D053583:Interleukin-1beta; D012996:Solutions; D014409:Tumor Necrosis Factor-alpha; C121557:hydroxyectoine; D018799:Intercellular Adhesion Molecule-1; C045628:ectoine; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D005978:Glutathione