Cardiovascular effects of (13S)-9_, 13_- epoxylabda-6_(19), 15(14)diol dilactone, a diterpenoid isolated from the organic extract of leonotis leonurus leaves, in anaesthetized normotensive rats

dc.contributor.advisorMugabo, Pierre
dc.contributor.advisorGreen, Ivan
dc.contributor.authorChibuzo, Obikeze Kenechukwu
dc.date.accessioned2014-06-23T10:53:42Z
dc.date.accessioned2024-05-15T07:16:46Z
dc.date.available2014-06-23T10:53:42Z
dc.date.available2024-05-15T07:16:46Z
dc.date.issued2009
dc.descriptionPhilosophiae Doctor - PhDen_US
dc.description.abstractPlants used in traditional medicines have served as sources of some of the drug compounds used in medicines today, and could still serve as leads for then development of new drugs to treat existing chronic diseases such as hypertension. This study was aimed at the isolation and identification of a cardio-active compound from L. leonurus, a plant commonly used in traditional medicines in South Africa for the treatment of hypertension and other cardiac problems. The possible mechanisms by which the isolated compound produced its effect on the cardiovascular system were explored using the anaesthetized normotensive rat model.Fractionation of the organic extracts of the leaves led to the isolation of a novel diterpene,(13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone (EDD) whose structure was elucidated using infra red (IR), nuclear magnetic resonance (NMR), mass spectroscopy(MS), and X-ray diffraction analysis. In anaesthetized normotensive male Wistar rats, EDD(0.5 mg/kg ā€“ 5.0 mg/kg; IV) produced slight non-significant decreases in systolic pressure(SP), diastolic pressure (DP), and mean arterial pressure (MAP) with the lower (0.5 mg/kgā€“ 2.0 mg/kg) doses, while significant increases in SP, DP and MAP occurred with the higher (3.0 mg/kg ā€“ 5.0 mg/kg) doses. All doses of EDD administered also produced significant decreases in heart rate (HR).Prazosin and reserpine pre-treatment abolished the vasoconstrictive effect of EDD,suggesting an indirect vasoconstrictive effect for EDD via the release of catecholamines.Atenolol pre-treatment led to increases in the negative chronotropic effect of EDD, while the positive chronotropic effect of dobutamine was significantly decreased by EDD,suggesting the involvement of the 1 adrenoceptor in the negative chronotropic effect of EDD. In animals pre-treated with verapamil, a cardio-selective Ca2+ channel blocker, no significant changes in HR occurred with all EDD doses, but HR values were significantly lower than those obtained with EDD in non pre-treated animals.The results of this study indicate that (13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone, a novel dilactone diterpene isolated from the leaves of L. leonurus has an effect on the cardiovascular system. EDD exhibits a dual effect on the cardiovascular system by producing a vasoconstrictive effect accompanied by bradycardia. The vasoconstrictive effect of EDD is probably due to the release of catecholamines, while the negative chronotropic effect is probably due to 1 adrenoceptor antagonism. Further studies are however required to fully determine the mechanism by which EDD produces its cardiovascular effects.en_US
dc.identifier.urihttps://hdl.handle.net/10566/15037
dc.language.isoenen_US
dc.subjectPlantsen_US
dc.subjectLeonotis leonurusen_US
dc.subjectDiterpenesen_US
dc.subjectAnaesthetized normotensive raten_US
dc.subjectCardiovascular effecten_US
dc.subjectNegative chronotropic effecten_US
dc.subjectVasoconstrictionen_US
dc.subjectBlood pressureen_US
dc.subjectHeart rateen_US
dc.titleCardiovascular effects of (13S)-9_, 13_- epoxylabda-6_(19), 15(14)diol dilactone, a diterpenoid isolated from the organic extract of leonotis leonurus leaves, in anaesthetized normotensive ratsen_US
dc.typeThesisen_US

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