Efeitos vasculares do oleorresina de Pterodon spp. Vogel (Fabaceae) e do seu diterpeno isolado (6α-acetoxi-7β-hidroxivouacapano-17β-oato de metila)
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2015-06-30
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Universidade Federal de Goiás
Resumo
The use of medicinal plants for the treatment of hypertension treatment has
been extensively studied. The genus Pterodon spp. Vogel (Fabaceae), popularly
known as sucupira, has five native Brazilian cerrado species. Studies demonstrated
that the Pterodon spp has antispasmodic and myorelaxant activities. Phytochemical
studies of sucupira found furanic diterpenes with vouacapanic skeleton in their fruits,
and the therapeutics activities from this gender are essentially attributed to these
compounds. The aim of this study was to evaluete the possible vasorelaxant activity
and the mechanisms of action of the oil-resin of sucupira (SOR) and its isolated
diterpene, methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate in isolated rat aorta
preparations. For comparison, verapamil curves (1 nM – 100 μM) were also obtained.
The results demonstrated that both, S0R (0 – 56 μg/mL) and the isolated diterpene (0
– 48 μg/mL) have a reversible concentration-dependent vasorrelaxant activity.
Endothelium denudation did not impair in the relaxant effect of both, ORS and the
diterpene. Aortic rings KCl-stimulated obtained a lower IC50 value than rings
contracted with phenylephrine under increasing concentrations of the tested
substances. The SOR and diterpene relaxant activity was not impaired when nonselective
K+ channels blockers were used (Tetraethylammonium). The use of
cyclopiazonic acid (SERCA inhibitor) indicated that there was no involvement of the
Ca2+ reuptake by sarcoplasmatic reticulum and the use of ODQ (an inhibitor of
guanylyl cyclase) and MDL-12,330A (an inhibitor of adenylyl cyclase), showed that
the 3, 5- cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine
monophosphate (cAMP) pathways were not involved in SOR relaxant activity.
However, the results indicate a possibly activity of the soluble guanylyl ciclase on
diterpene relaxant effect. Both, SOR and isolated diterpene inhibited the CaCl2
induced contractions in aortic rings stimulated with phenylephrine (0.1μM) or Bay
K8644 (a Cav1.2 channel activator; 1μM) and by depolarizing KCl solution (40 mM).
Computational molecular docking studies demonstrated that the vasodilator effect of
diterpene relies on blocking the Cav1.2 channel, and patch clamp results showed that
diterpene substantially decreased the ionic current through Cav1.2 in freshly
dissociated vascular smooth muscle cells. These findings suggest that SOR and its
isolated diterpene induce endothelium-independent vascular relaxation by blocking
the L-type Ca2+ channel (Cav1.2).
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Citação
REIS, C. F. Efeitos vasculares do oleorresina de Pterodon spp. Vogel (Fabaceae) e do seu diterpeno isolado (6α-acetoxi-7β-hidroxivouacapano-17β-oato de metila). 2015. 91 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2015.