Anti-inflammatory activity of Mitraphylline isolated from Uncaria tomentosa bark |
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Authors: | R Rojas-Duran G González-Aspajo C Ruiz-Martel G Bourdy VH Doroteo-Ortega J Alban-Castillo G Robert P Auberger E Deharo |
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Institution: | 1. Unidad de Investigación en Productos Naturales, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, SMP, Lima, Peru;2. Université de Toulouse, Université Paul Sabatier, Pharma-Dev UMR 152, Faculté de Pharmacie, 35 Chemin des maraîchers, F-31062 Toulouse Cedex 9, France;3. Institut de Recherche pour le Développement (IRD), Pharma-Dev UMR 152, Faculté de Pharmacie, 35 Chemin des maraîchers, F-31062 Toulouse Cedex 9, France;4. Museo de Historia Natural, Universidad Nacional Mayor de San Marcos, Av. Arenales 1256, Jesus Maria, Lima, Peru;5. INSERM U1065 (C3M) Team 2 Cell Death, Differentiation, Inflammation and Cancer, 151 route de Saint Antoine de Ginestière, 06204 Nice Cedex 3, France |
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Abstract: | Ethnopharmacological relevanceUncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) is widely used by populations living in South America to treat many ailments associated with inflammatory disorders. Mitraphylline was shown to be the major pentacyclic oxindolic alkaloid present in the bark chloroformic extract of this plant. Its activity against cytokines involved in inflammation process was tested in a murine model in vivo.Materials and methodsMice received mitraphylline once a day for 3 days at 30 mg/kg/day by oral route. Then, they were subjected to bacterial lipopolysaccharide (LPS) endotoxin (15 mg/kg) and the LPS-induced production of 16 different cytokines was determined by Elisa multiplex. Control group received dexamethasone orally at 2 mg/kg/day. Toxicity on K565 cells and murine peritoneal macrophages, in vitro, at doses up to 100 μM was monitored by XTT-colorimetric assay.Results and conclusionsFor the first time mitraphylline was tested in vivo against a large range of cytokines that play a crucial role in inflammation. Mitraphylline inhibited around 50% of the release of interleukins 1α, 1β, 17, and TNF-α. This activity was similar to dexamethasone. It also reduced almost 40% of the production of interleukin 4 (IL-4) while the corticoid did not. Lastly it did not show any toxicity on K565 cells nor murine macrophages at doses up to 100 μM. |
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Keywords: | IL Interleukin LPS Lipopolysaccharide THP-1 monocytic cells (ATCC TIB-202) TNF tumor necrosis factor XTT sodium 3&prime -[1-(phenylaminocarbonyl)-3 4-tetrazolium]-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate |
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