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.
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-alpha) as a mediator of inflammation and apoptosis were measured in the colon homogenate. Treatment by DSS increased bowel LP, NO, and TNF-alpha 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-alpha 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.
Laboratory of Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Noushin
N
Amini-Shirazi
Asieh
A
Hoseini
Akram
A
Ranjbar
Azadeh
A
Mohammadirad
Pooneh
P
Khoshakhlagh
Nargues
N
Yasa
Mohammad
M
Abdollahi
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D019686:Lamiaceae / Q000737:chemistry*; D008519:Medicine, Traditional; D051379:Mice; D018384:Oxidative Stress; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000378:metabolism / Q000627:therapeutic use; D010946:Plants, Medicinal / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D016166:Free Radical Scavengers; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate