Inhibition of Tumor Necrosis Factor and Nitrosative/Oxidative Stresses by Ziziphora Clinopoides (Kahlioti); A Molecular Mechanism of Protection Against Dextran Sodium Sulfate-Induced Colitis in Mice

Abstract

Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune genetic and environmental factors. The authors were interested in examining the protective effect of Ziziphora clinopoides methanolic extract, an Iranian folk herbal medicine, on inflammatory mediators in experimental colitis. Colitis in NMRI mice was induced by oral administration of dextran sodium sulfate (DSS, 3%). Z. clinopoides was administrated orally at doses of 75, 150, and 300 mg/kg/day for 7 days. The level of lipid peroxidation (LP), total antioxidant capacity (TAC), total thiol molecules (TTM), antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT), and nitric oxide (NO) as a marker of nitrosative stress, and tumor necrosis factor alpha (TNF-α) as a mediator of inflammation and apoptosis were measured in the colon homogenate. Treatment by DSS increased bowel LP, NO, and TNF-α while decreasing TAC, SOD, CAT, and TTM. All measured parameters were improved by Z. clinopoides treatment and reached close to normal levels. The present study further supports the role of oxidative/nitrosative stresses and TNF-α in the pathogenesis of colitis and protective effects of this herb. The data are promising for further preclinical studies directed towards understanding mechanism of action and cross-species and cross-model comparisons for potential protective effects.

KEYWORDS:

• Ziziphora clinopoides
• Oxidative stress
• Nitrosative stress
• TNF-α
• Inflammatory bowel disease
• Dextran sodium sulfate
• Colon

This study was supported by a grant from TUMS (85–01-33–3645).