title: Tetra-acetylajugasterone a new constituent of Vitex cienkowskii with vasorelaxant activity.
abstract: Tetra-acetylajugasterone C (TAAC) was found to be one of the naturally occurring compounds of the Cameroonian medicinal plant Vitex cienkowskii which is responsible for a vasorelaxant activity of an extract of this plant. The evaluation of the underlying mechanisms for the relaxing effect of TAAC was determined using aortic rings of rats and mice. TAAC produced a concentration-dependent relaxation in rat artery rings pre-contracted with 1μM noradrenaline (IC50: 8.40μM) or 60mM KCl (IC50: 36.30μM). The nitric oxide synthase inhibitor l-NAME (100μM) and the soluble guanylate cyclase inhibitor ODQ (10μM) significantly attenuated the vasodilatory effect of TAAC. TAAC also exerted a relaxing effect in aorta of wild-type mice (cGKI(+/+); IC50=13.04μM) but a weaker effect in aorta of mice lacking cGMP-dependent protein kinase I (cGKI(-/-); IC50=36.12μM). The involvement of calcium channels was studied in rings pre-incubated in calcium-free buffer and primed with 1μM noradrenaline prior to addition of calcium to elicit contraction. TAAC (100μM) completely inhibited the resulting calcium-induced vasoconstriction. The same concentration of TAAC showed a stronger effect on the tonic than on the phasic component of noradrenaline-induced contraction. This study shows that TAAC, a newly detected constituent of Vitex cienkowskii contributes to the relaxing effect of an extract of the plant. The effect is partially mediated by the involvement of the NO/cGMP pathway of the smooth muscle but additionally inhibition of calcium influx into the cell may play a role.
authors.affiliation: Department of Animal Biology, Faculty of Science, University of Douala, P.O. Box 24157, Douala, Cameroon. Electronic address: alainberd@yahoo.fr.
authors.forename: Alain Bertrand
authors.initials: AB
authors.lastname: Dongmo
authors.affiliation: Department of Chemistry, University of Dschang, P.O. Box 371, Dschang, Cameroon.
authors.forename: Pepin Alango
authors.initials: PA
authors.lastname: Nkeng-Efouet
authors.affiliation: Institute of Forestry, Tribhuvan University, Pokhara Campus, P.O. Box 43, Pokhara, Nepal.
authors.forename: Krishna Prasad
authors.initials: KP
authors.lastname: Devkota
authors.affiliation: Institute of Pharmacology and Toxicology, Technical University of Munich, Biedersteiner Str. 29, 80802 Munich, Germany.
authors.forename: Jörg W
authors.initials: JW
authors.lastname: Wegener
authors.affiliation: Chemistry Department, Organic and Bioorganic Chemistry, Bielefeld University, P.O. Box 100131, 33501 Bielefeld, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
authors.affiliation: Institute of Pharmaceutical Biology, Butenandt Str. 5 - 13 B, 81377 Munich, Germany.
authors.forename: Hildebert
authors.initials: H
authors.lastname: Wagner
authors.affiliation: Institute of Pharmacology and Toxicology, Technical University of Munich, Biedersteiner Str. 29, 80802 Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vierling
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D000071756:Soluble Guanylyl Cyclase; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*; D020950:Vitex / Q000737:chemistry*
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; C000594077:tetra-acetylajugasterone C; D009569:Nitric Oxide; D004441:Ecdysterone; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
keywords: Aortic smooth muscle; Nitric oxide; Relaxation; Tetra-acetylajugasterone C; Vitex cienkowskii; cGKI; cGMP