Bioassay-guided isolation of anti-inflammatory and antinociceptive principles from a folk remedy, Rhododendron ponticum L. leaves

Ethnopharmacological relevance: Rhododendron ponticum L (Ericaceae) is used for the treatment of inflammatory diseases and to alleviate rheumatic pain and against toothache in Turkish traditional medicine. Aim of the study: To evaluate the anti-inflammatory and antinociceptive effects of Rhododendron ponticum leaves using in vivo models, and isolation and chemical characterization of the biologically active constituents through bioassay-guided fractionation procedures. Material and Methods: Carrageenan-induced hind paw edema model was used for anti-inflammatory activity and p-benzoquinone induced abdominal contractions model for the antinociceptive activity assessment. Results: The ethylacetate fraction displayed marked anti-inflammatory (28.4-40.7% inhibition) and antinociceptive (50.7% inhibition) effects as compared to reference compounds. Through bioassay-guided fractionation and isolation procedures flavonol glycosides [a mixture of hyperoside and isocluercitrin (1) and quercitrin (2)] along with one flavanone glycoside [6-C-glycosylnaringenin (3)] were isolated as the active ingredients of ethylacetate extract against carrageenan-induced edema and p-benzoquinone-induced writhes and their structures were elucidated by spectral techniques. I and 2 also showed a significant anti-inflammatory activity against 12-0-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema model. Conclusion: Results of the present study supported the utilization of the plant in Turkish folk medicine and revealed that flavones are the major anti-inflammatory and antinociceptive principles of the leaves. (C) 2008 Elsevier Ireland Ltd. All rights reserved.