Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice.
Quercetin is a plant-derived flavonoid widely known by its anti-oxidant and anti-inflammatory properties, but its oral bioavailability is very poor and this becomes difficult to assess its therapeutic potential. Here we have compared the anti-inflammatory effect of quercetin-loaded microemulsion (QU-ME) and quercetin suspension (QU-SP) in an experimental model of airways allergic inflammation. Mice received daily oral doses of QU-ME (3 or 10mg/kg; in an oil-in-water microemulsion content 0.02:0.2:1 of lecithin:castor oil:Solutol HS15((R))), QU-SP [10mg/kg, in carboxymethylcellulose (CMC) 0.5% in water] or vehicle from the 18th to the 22nd day after the first immunization with ovalbumin (OVA). Dexamethasone was used as positive control drug. Every parameter was evaluated in the 22nd day (24h after the second OVA-challenge). We have also tried to assess by HPLC-MS a quercetin metabolite in the blood of rats treated with QU-SP or QU-ME. QU-ME was better orally absorbed when compared with QU-SP. Furthermore, oral administration of QU-SP failed to interfere with leukocyte recruitment, while QU-ME inhibited in a dose-dependent way, the eosinophil recruitment to the bronchoalveolar lavage fluid (BALF). QU-ME also significantly reduced both IL-5 and IL-4 levels, but failed to interfere with CCL11, IFN-gamma and LTB(4) levels. In addition, QU-ME oral treatment inhibited the nuclear transcription factor kappa B (NF-kappaB) activation, P-selectin expression and the mucus production in the lung. The present results show that QU-ME exhibits pronounced anti-inflammatory properties in a murine model of airways allergic inflammation and suggest that it might present therapeutic potential for the airways inflammatory diseases management.
Rogerio
Alexandre P
AP
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Centro de Ciências Biológicas, Florianópolis, SC, Brazil.
Dora
Cristiana L
CL
Andrade
Edinéia L
EL
Chaves
Juliana S
JS
Silva
Luis F C
LF
Lemos-Senna
Elenara
E
Calixto
João B
JB
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010316:Particle Size; D011794:Quercetin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013535:Suspensions
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D004655:Emulsions; D018836:Inflammation Mediators; D016328:NF-kappa B; D019007:P-Selectin; D013535:Suspensions; D011794:Quercetin