Anti-inflammatory activity of Mitraphylline isolated from Uncaria tomentosa bark

Ethnopharmacological relevance: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) iswidely used by populations living in South America to treat many ailments associated withinflammatory disorders. Mitraphylline was shown to be the major pentacyclic oxindolic alkaloidpresent in the bark chloroformic extract of this plant. Its activity against cytokines involved ininflammation 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 oralroute. Then, they were subjected to bacterial lipopolysaccharide (LPS) endotoxin (15 mg/kg) and theLPS-induced production of 16 different cytokines was determined by Elisa multiplex. Control groupreceived dexamethasone orally at 2 mg/kg/day. Toxicity on K565 cells and murine peritoneal macro-phages, in vitro, at doses up to 100 mM was monitored by XTT-colorimetric assay.Results and conclusions: For the first time mitraphylline was tested in vivo against a large range ofcytokines that play a crucial role in inflammation. Mitraphylline inhibited around 50% of the release ofinterleukins 1a, 1b, 17, and TNF-a. This activity was similar to dexamethasone. It also reduced almost40% of the production of interleukin 4 (IL-4) while the corticoid did not. Lastly it did not show anytoxicity on K565 cells nor murine macrophages at doses up to 100 mM.