title: Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats.
abstract: The aim of the present study was to investigate the therapeutic effect and mechanism of 3,4-oxo-isopropylidene-shikimic acid (ISA) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. (50, 100, 200 mg/kg) was administered for 14 days, 1 day after the induction of colitis by TNBS. The colonic injury and inflammation were assessed by macroscopic damage scores and myeloperoxidase (MPO) activity. Malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma were measured with biochemical methods. Prostaglandin E2 (PGE2) level in colon was determined by radioimmunoassay. Expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), inhibitor kappa B-alpha (IκBα) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry. Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with TNBS, which was manifested as the significant increase in colon mucosal damage index, MPO activity, levels of MDA, NO and PGE2, as well as the expressions of iNOS, COX-2 and NF-κB p65 proteins in the colonic mucosa, and the significant decrease in expressions of IκBα proteins in the colonic mucosa. However, these parameters were found to be significantly ameliorated in rats treated with ISA at given doses, especially at 100 mg/kg and 200 mg/kg. Administration of ISA may have significant therapeutic effects on experimental colitis in rats, probably due to its mechanism of antioxidation, its inhibition of arachidonic acid metabolism and its modulation of the IκBα/NF-κB p65 expression.
authors: Department of Pharmacy, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Jianfeng
authors: J
authors: Xing
authors: Cuiyu
authors: C
authors: You
authors: Kai
authors: K
authors: Dong
authors: Jinyao
authors: J
authors: Sun
authors: Haisheng
authors: H
authors: You
authors: Yalin
authors: Y
authors: Dong
authors: Jianning
authors: J
authors: Sun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012765:Shikimic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage
chemical_list: C479295:3,4-oxoisopropylideneshikimic acid; D000975:Antioxidants; D016328:NF-kappa B; D012765:Shikimic Acid; D009569:Nitric Oxide; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone