RESUMEN
Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol-free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g(-1)) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate-salt and N(G)-nitro-L-arginine methyl ester (L-NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre-contracted with norepinephrine, bolus injections of GSE induced endothelium-dependent vasodilatation that was substantially inhibited by L-NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration-dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.
Asunto(s)
Antihipertensivos/uso terapéutico , Antioxidantes/uso terapéutico , Flavonoides , Hipertensión/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Vasodilatadores/uso terapéutico , Vitis/química , Animales , Antihipertensivos/farmacología , Antioxidantes/farmacología , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Técnicas In Vitro , Peroxidación de Lípido/efectos de los fármacos , Masculino , Arteria Mesentérica Superior/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Fenoles/análisis , Extractos Vegetales/química , Polímeros/análisis , Polifenoles , Ratas , Ratas Wistar , Factores de Tiempo , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Agua , VinoRESUMEN
Toxicity of an aqueous extract prepared from Echinodorus macrophyllus dried leaves, a plant used in folk medicine to treat inflammation and kidney malfunctions, was estimated by different bioassays. Mutagenicity of the aqueous extract was evaluated in the Salmonella/microsome assay (TA97a, TA98, TA100 and TA102 strains), with or without metabolic activation. No mutagenic activity (lyophilized extract tested up to 50 mg/plate) could be detected to any of the tester strain. Furthermore, no cytotoxic effect has been observed when a crude extract of E. macrophyllus (up to 7.5 mg/ml) was tested on the exponential growth of hepatoma and normal kidney epithelial cells in culture. Toxicity of E. macrophyllus was also evaluated in male Swiss mice after 6 weeks of continuous ingestion of the aqueous extract in drinking water. Average daily ingested doses were 3, 23 and 297 mg/kg for a lyophilized extract, and 2200 mg/kg for a crude extract, with dose two being equivalent to the daily dose recommended to humans. At the end of the treatment, all animals revealed a deficit in final body weight ranging from 5 to 47%. Biochemical analysis of the plasma revealed some minor alterations indicating subclinical hepatic toxicity. Genotoxic effect on liver, kidney and blood cells has been also evaluated by the comet assay, being negative to liver and blood cells. However, DNA analyses of the kidney cells detected some genotoxic activity for the highest dose tested of E. macrophyllus extract, either lyophilized or crude. On the other hand, exposure dose of 23 mg/kg, equivalent to the daily dose recommended to humans, did not revealed any genotoxic effect and hence this herb seems to be safe to human organism.