6533b837fe1ef96bd12a3134
RESEARCH PRODUCT
Bacteria-Derived Compatible Solutes Ectoine and 5α-Hydroxyectoine Act as Intestinal Barrier Stabilizers to Ameliorate Experimental Inflammatory Bowel Disease
Mohamed T. KhayyalHeba Abdel-azizOlaf SchernerW WadieThomas Efferthsubject
MaleColonInterleukin-1betaPharmaceutical SciencePharmacologyEctoineInflammatory bowel diseaseAnalytical Chemistrychemistry.chemical_compoundDrug DiscoverymedicineAnimalsHumansRats WistarColitisPeroxidasePharmacologyBacteriaMolecular StructurebiologyTumor Necrosis Factor-alphaChemistryOrganic ChemistryAmino Acids DiaminoGlutathioneColitisInflammatory Bowel DiseasesIntercellular Adhesion Molecule-1medicine.diseasebiology.organism_classificationGlutathioneRatsIntestinesSolutionsTrinitrobenzenesulfonic AcidComplementary and alternative medicineBiochemistryMyeloperoxidasebiology.proteinMolecular MedicineEgyptOsmoprotectantTumor necrosis factor alphaBacteriadescription
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.
year | journal | country | edition | language |
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2015-05-28 | Journal of Natural Products |