Ethnopharmacological relevance: Uncaria 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 methods: Mice 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 conclusions: For 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.
Bibliographical noteFunding Information:
German Gonzalez was awarded a fellowship from the Coopération Technique Belge. The authors are grateful to CONCYTEC (Project 334–2007-CONCYTEC-OAJ ) for its financial support. The authors have written this article under the auspices of CaP (Chemotherapy against Parasites/Consortium antiParasitaire). We are indebt to Dr. Brian Gadd and Stéphane Bertani, from the Cell, Molecular, and Developmental Biology Department of the University of California Riverside for discussions and in-depth reading of this manuscript.
- Pentacyclic oxindolic alkaloids
- Traditional medicine
- Uncaria tomentosa