RESUMO
Diosgenin is a phytoestrogen and a constituent of Dioscorea. It has several biological effects, and some of them are anti-inflammatory, antidiabetic, antitumor, and vasodilatory. The present study investigated both the vasorelaxing and antioxidant mechanisms of diosgenin in isolated rat aortic rings. Female rats weighing 200-220 g were subjected to sham or OVX operations at 8 weeks of age. Ovariectomy was performed for menopause induction after anesthesia. Diosgenin (10-9 M-3 × 10-4 M) produced a concentration-dependent relaxation in aortic rings precontracted with phenylephrine (1 µM), exhibiting Emax value of 55.34% ± 7.7% (in endothelium-intact rings) and Emax value of 30.30% ± 5.7% (in endothelium-denuded rings). In the endothelium-intact rings, the vasorelaxing effect of diosgenin was reduced by NG-nitro-l-arginine methyl ester (L-NAME) (100 µM), atropine (1 µM), indomethacin (10 µM), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (10 µM), 4-aminopyridine (1 mM), tetraethylammonium (3 mM), glibenclamide (10 µM), apamin (10 µM), and Tiron (1 µM). Diosgenin (10-5 M) inhibited the contractions induced by cumulative addition of phenylephrine (10-9-10-5 M). The 28-days treatment with diosgenin (50 mg/kg, v.o.) did not imply changes in the myeloperoxidase parameter, but increased significantly, levels of glutathione, superoxide dismutase, and nitric oxide, as well as reduced the concentration of malondialdehyde related to lipid peroxidation. Our results suggest that diosgenin induced relaxation in aortic rings via an endothelium-dependent pathway, which involves the EDRF, the opening of potassium channels and antioxidant action.
Assuntos
Diosgenina/administração & dosagem , Menopausa/efeitos dos fármacos , Fitoestrógenos/administração & dosagem , Extratos Vegetais/administração & dosagem , Vasodilatadores/administração & dosagem , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Dioscorea/química , Diosgenina/química , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Glutationa/metabolismo , Humanos , Técnicas In Vitro , Masculino , Menopausa/metabolismo , Nitritos/metabolismo , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Fitoestrógenos/química , Extratos Vegetais/química , Canais de Potássio/metabolismo , Ratos , Ratos Wistar , Vasodilatadores/químicaRESUMO
The study evaluated the vasorelaxant effect induced by the ethanolic extract of the leaves of Zanthoxylum rhoifolium Lam (EEtOH-Zr/leaves). Wistar rats were treated with the leaf extract containing a single dose of 2,000 mg / kg, v.o. After 14 days, the animals were anesthetized for blood collection and subsequent analysis of the biochemical parameters; they were then euthanized (sodium pentobarbital-100 mg/kg, i.p.) for the removal and morphological analysis of the heart, lung, liver and kidney. The vasorelaxation activity the and vascular reactivity of EEtOH-Zr/leaves were evaluated on artery mesenteric rings isolated from rats. The extract showed no signs of toxicity and no significant difference in the values of the biochemical parameters between the control group and the group of treated animals. In the evaluation of pharmacological activity in the smooth muscle, the EEtOH-Zr/leaves caused vasorelaxant effect on the tonic contraction induced by phenylephrine in mesenteric artery preparations in the presence (pD2=2.17±0.05 µg/mL; Emax=99.8±5.2%) and absence (pD2=2.14±0.05 µg/mL; Emax=95.3±6.4%) of the vascular endothelium. Oral administration of EEtOH-Zr/leaves reduced the contraction induced by the cumulative addition of PHE. It is concluded that the EEtOH-Zr/leaves promote vasorelaxation and reduce vascular reactivity of adrenergic alpha-1 agonist in the mesenteric artery. The results did not show toxic effects of the extract.