Evaluation of the anti-inflammatory and analgesic activity of Me-UCH9, a dual cyclooxygenase-2/5-lipoxygenase inhibitor
| Autor: | C. León, José N. Domínguez, María Luisa Ferrándiz, M. J. Alcaraz, Amparo Araico, María Carmen Terencio |
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| Rok vydání: | 2007 |
| Předmět: |
Chalcone
medicine.drug_class Stereochemistry medicine.medical_treatment Analgesic Anti-Inflammatory Agents Arthritis Pharmacology Carrageenan General Biochemistry Genetics and Molecular Biology Anti-inflammatory Mice chemistry.chemical_compound Chalcones Oral administration medicine Animals Edema Humans Cyclooxygenase Inhibitors Lipoxygenase Inhibitors Enzyme Inhibitors Rats Wistar General Pharmacology Toxicology and Pharmaceutics Analgesics Dose-Response Relationship Drug biology business.industry Zymosan General Medicine medicine.disease Arthritis Experimental Rats chemistry Cyclooxygenase 2 biology.protein Female Cyclooxygenase business Prostaglandin E |
| Zdroj: | Life Sciences. 80:2108-2117 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2007.03.017 |
| Popis: | Recently, we reported the dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) activity by some phenylsulphonyl urenyl chalcone derivatives. 2,4-dichloro-4′ N [ N ′(4″methylphenylsulphonyl)urenyl] chalcone (Me-UCH9), was selected in the present study to determine its potential anti-inflammatory and analgesic effect after oral administration in several animal models related to the activation of COX-2 and 5-LO pathways. In the zymosan stimulated mouse air pouch model, Me-UCH9, reduced in a dose-dependent manner leukotriene B 4 (LTB 4 ) levels in pouch exudates obtained at 4 h, as well as prostaglandin E 2 (PGE 2 ) generated through COX-2 activation at 24 h. Tumor necrosis factor α (TNF-α) and myeloperoxidase activity were also strongly inhibited in this model. Me-UCH9 significantly reduced granulome size and vascular index determined in the murine air pouch granuloma model of angiogenesis. In the carrageenan-induced paw edema, this compound inhibited inflammatory response and pain, as well as PGE 2 and LTB 4 content in paw edematous fluid. Analgesic properties were corroborated in the murine phenyl- p -benzoquinone-induced writhing test. Finally, Me-UCH9 exerted anti-inflammatory effects in the chronic model of rat adjuvant-induced arthritis, both inhibiting paw swelling and reducing PGE 2 content. Our findings confirm that Me-UCH9 can modulate inflammatory and nociceptive responses in relation to the dual inhibition of COX-2 and 5-LO activities presented by this compound. |
| Databáze: | OpenAIRE |
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