The intestinal anti-inflammatory effect of quercitrin is associated with an inhibition in iNOS expression.
Quercitrin, 3-rhamnosylquercetin, is a bioflavonoid with antioxidant properties, which exerts anti-inflammatory activity in experimental colitis. In the present study, different in vivo experiments were performed in order to evaluate the mechanisms of action involved in this effect, with special attention to its effects on proinflammatory mediators, including nitric oxide (NO). Experimental colitis was induced in female Wistar rats by incorporation of dextran sodium sulfate (DSS) in drinking water. Oral treatment of quercitrin (1 or 5 mg kg(-1) day(-1)) to colitic rats ameliorated the evolution of the inflammatory process induced when administered in a preventative dosing protocol. When quercitrin (1 mg kg(-1) day(-1)) was administered on established colitis, it facilitated the recovery of the inflamed mucosa. The beneficial effects exerted by quercitrin were evidenced both histologically and biochemically, and were associated with an improvement in the colonic oxidative status, altered as a consequence of the colonic insult induced by DSS. In addition, a reduction of colonic NO synthase activity was observed, probably related to a decreased expression in the inducible form of the enzyme via downregulation in the colonic activity of the nuclear factor-kappaB. Immunohistochemical studies showed that quercitrin treatment reduced macrophage and granulocyte infiltration in the inflamed tissue.
Camuesco
Desiree
D
Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
Comalada
Monica
M
Rodríguez-Cabezas
M Elena
ME
Nieto
Ana
A
Lorente
Maria D
MD
Concha
Angel
A
Zarzuelo
Antonio
A
Gálvez
Julio
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004791:Enzyme Inhibitors; D005260:Female; D005455:Fluorescent Antibody Technique; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007975:Leukotriene B4 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D007975:Leukotriene B4; D009569:Nitric Oxide; D016264:Dextran Sulfate; D011794:Quercetin; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000469:Alkaline Phosphatase; D005978:Glutathione