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Pentacyclic triterpenoids and ceramide mediate the vasorelaxant activity of Vitex cienkowskii via involvement of NO/cGMP pathway in isolated rat aortic rings |
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| Authors: | Dongmo Alain Bertrand Azebaze Anatole Guy Blaise Donfack Flaure Metchi Dimo Théophile Nkeng-Efouet Pepin Alango Devkota Krishna Prasad Sontia Bruno Wagner Hildebert Sewald Norbert Vierling Wolfgang |
| Affiliation: | a Department of Animal Biology, Faculty of Science, University of Douala, P.O. Box 24157, Douala, Cameroon b Department of Chemistry, Faculty of Science, University of Douala, P.O. Box 24157, Douala, Cameroon c Department of Animal Biology, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaounde, Cameroon d Department of Chemistry, University of Dschang, P.O. Box 371, Dschang, Cameroon e Chemistry Department, Organic and Bioorganic Chemistry, Bielefeld University, P.O. Box 100131, 33501 Bielefeld, Germany f Institute of Pharmacology and Toxicology, Technical University of Munich, Biedersteinerstr. 29, 80802 Munich, Germany g Institute of Pharmaceutical Biology, Butenandtstr. 5-13, 81377 Munich, Germany i Institute of Forestry, Tribhuvan University Pokhara Campus, P.O. Box 43, Pokhara, Nepal |
| Abstract: | Ethnopharmacological relevanceVitex cienkowskii Kotschy & Peyritsch is a deciduous tree, prescribed by Cameroonian traditional healers as one of the most popular plant widely used in many disorders including cardiovascular diseases. The preliminary pharmacological studies carried out on Vitex cienkowskii showed its vasorelaxant activities on guinea-pig aortic rings.Aim of the studyThe present work evaluated the vasorelaxant activity of extract and isolated compounds from Vitex cienkowskii.Materials and methodsRat aortic rings were used to evaluate the in vitro vascular effect of the extract. The antioxidant activity was determined by measuring the reduction of the free radical 1,1-diphenyl-1-picryl-hydrazyl (DPPH).ResultsVitex cienkowskii induced significant relaxation in a concentration- and endothelium-dependent manner (EC50 = 12.12 μg/ml, CH2Cl2-MeOH, 1:1) and did not produce a vasorelaxant effect on contraction evoked by KCl (60 mM). In order to determine its mode of action, Vitex cienkowskii-induced relaxant effect was evaluated in the presence of indomethacin (10 μM), L-NAME (100 μM), ODQ (1 μM) and SQ22356 (100 μM). Relaxation was significantly blocked by L-NAME and ODQ. These results indicate that Vitex cienkowskii-mediated relaxation is endothelium dependent, probably due to NO release, and the consequent activation of vascular smooth muscle soluble guanylate cyclase (sGC), a signal transduction enzyme that forms the second messenger cGMP. Bio-guided study of Vitex cienkowskii allowed the isolation of the known pentacyclic triterpenoids and a ceramide. It is the first report of salvin A, maslinic acid and a ceramide from Vitex cienkowskii. The activity induced by these compounds indicated that they may be partly responsible for the vasorelaxant effect of the plant extract.A dose of 40 mg/kg of CH2Cl2-MeOH (1:1) extract administered intravenously induced a decrease of mean arterial pressure but did not affect the heart rate. Moreover the plant extracts were found to be highly active in the DPPH radical scavenging assay.ConclusionVitex cienkowskii extract possesses antioxidant property, vasorelaxing, and hypotensive effect linked to the endothelium related factors, where nitric oxide is involved. |
| Keywords: | NO, nitric oxide L-NAME, NG-nitro-L-arginine-methyl ester DPPH, 1,1-diphenyl-1-picryl-hydrazyl TLC, thin-layer chromatography ODQ, 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one SQ22536, 9-(tetrahydro-2-furanyl)-9H-purine-6-amine |
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