Atividades de um extrato hidroalcoólico padronizado de Ampelozizyphus amazonicus Ducke nativa de Manacapuru/AM mecanismo do efeito hipotensor em roedores

Abstract

In Amazonian region, Ampelozizyphus amazonicus Ducke, known as saracura-mirá or cerveja de índio , is used to treat gastrointestinal disorders, as an antidote to snake venoms and to prevent malaria. Chemical studies report the triterpenic saponins as the main constituents, however, chemical standardization of the extracts are not described. The anti-plasmodium effect of the aqueous and ethanolic extracts was not observed neither in vitro in cultured P. falciparum, nor in vivo in mice infected with P. berghei and chickens infected with P. gallinaceum. The isolated compounds were not tried in these experiments. Studies on systemic effects of the extracts and dose-effect correlation are scarce. For these reasons, this work proposes the chemical standardization of the extract and the evaluation of the secondary pharmacology, mainly in the cardiovascular system. The plant was collected in Manacapuru (AM). Due to the high concentration of saponins in stems, the extraction was performed in ethanol 50 % and latter partitioned with n-butanol for the separation of the chemical compounds in preparative HPLC. Six majoritary compounds, identified by the peaks retention time and concentration in sample were used as references. The hydroalcoholic extract and its butanolic fraction have shown a slight CNS depressant effect demonstrated by the potentiation of the sleeping time induced by pentobarbital and ethylic ether. The extracts also produced anxiolytic-like effect in the plus maze test and depression in the tail suspension test in mice. Antinociceptive and anti-inflammatory effects were detected in paw edema induced by formalin and carrageenan in rats. FBut protected the gastric mucosa against cold stress or ethanol induced gastric damage, but not against indomethacin-induced gastric damage. FBut inhibited the gastric secretion in vivo in mice and the H+-K+-ATPase in vitro, suggesting an anti-secretory effect. FBut showed hypotensive effect in rats chronically treated per os and in anesthetized rats after e.v. injection. The atrial automatism was not altered, but negative inotropic effect was observed in rat myocardium in vitro. In rat aorta, FBut relaxed the adrenergic tonus. This effect was partially blocked by L-NAME pre-incubation or mechanical destruction of the endothelium. In rat isolated jejunum, the EC50 of the ACh was increased, however, the maximum contraction was not altered. In rat isolated vas deferens adrenergic contraction, the FBut showed non-competitive antagonistic effect. In depolarized vas deferens, the FBut decreased the contraction induced by CaCl2, suggesting a calcium influx blockade. In rat isolated diaphragm, the directly or indirectly contractions induced by electrical stimulation of the muscle was not altered. In mammalian P-type ATPases, FBut inhibited the gastric H+,K+-ATPase, but did not inhibit the Ca2+-ATPase in vitro. The results indicate that hypotension produced by FBut seems to be related to the relaxation of the adrenergic vascular tonus, possibly due to the activation of the NO synthesis in the endothelial cells. The FBut effects in rat aorta and smooth muscles indicate that other vasodilatory mechanism(s) may be involved, probably calcium channel blockade in vascular smooth muscle.