RESUMO
Bioassay-directed fractionation of the methanolic extract of seeds of Casimiroa edulis led to the isolation of seven constituents with cardiovascular activity, namely the new compound synephrine acetonide and the known compounds N-monomethylhistamine, N,N-dimethylhistamine, proline, N-methylproline, gamma-aminobutyric acid and casimiroedine. In anesthetized rats, both histamine derivatives produced transient hypotension mediated via H1-histaminergic receptors and in the case of N,N-dimethylhistamine, via nitric oxide release. Synephrine acetonide produced transient hypertension and tachycardia, mediated via alpha- and alpha- and beta-adrenergic receptores, respectively. The chromatographic zone containing N-methyproline, proline and gamma-aminobutyric acid elicited marked and prolonged hypotension. Finally, casimiroedine did not modify the blood pressure of anesthetized rats, but lowered it persistently in anesthetized guinea pigs. It was concluded that hypotension produced by C. edulis is due to several active components. The immediate effect can be attributed to the histamine derivatives acting on H1-receptors. More prolonged hypotension would be produced by the mixture of amino acids through an unknown mechanism, as well as by casimiroedine, possibly by activation of H3-receptors. Hypotension is partially offset by synephrine acetonide through adrenergic mechanisms.
Assuntos
Anti-Hipertensivos/farmacologia , Histamina/análogos & derivados , Medicina Tradicional , Plantas Medicinais/química , Sementes/química , Sinefrina/análogos & derivados , Animais , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Cobaias , Frequência Cardíaca/efeitos dos fármacos , Masculino , Metilistaminas/isolamento & purificação , Metilistaminas/farmacologia , México , Nucleosídeos/isolamento & purificação , Nucleosídeos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-ß-2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only (R)-(+ )-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-ß-methyl-2-naphthaleneethyl 6-methoxy-α-methyl-2-naphthaleneacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus.
RESUMO
A collection of Montanoa (Cerv) specimens was conducted throughout Mexico. Twenty-one specimens were classified, some of them grown in the greenhouse and transplanted in an agricultural experimental field station in the Valley of Mexico. In vitro uterotonic potency was assayed and the results expressed as equivalents of oxytocine, by using estrogenized guinea pig uterine strips. A great variation of uterotonic potency was observed among the wild plants. A clear decrease and uniformity of uterotonic potency was found in plants grown in the experimental field. The study points out the importance of ecological variations in expression of the plant's biological activity.
PIP: 21 specimens of the zoapatle Montanoa (Cerv) plant were collected from sites throughout Mexico with a variety of climatic, humidity, soil composition, and altitude conditions to assess their uterotonic properties. Some plants were then grown in an agricultural experimental field station of the National Institute of Agricultural Research, where all the variables were known, allowing for a valid comparison between species and plants. In vitro uterotonic potency was assayed and the results expressed as equivalents of oxytocin. The wild plants were found to vary greatly in uterotonic potency, perhaps reflecting differences in ecological conditions. The most active uterotonic zoapatle aqueous crude extract was the Montanoa frutescens, and the least active was M. mollissima, the former having approximately 4 times the uterotonic potency of the latter. The plants grown in the agricultural field station showed a considerable decrease in uterotonic potency, but valid comparisons must await assay in winter to match the stage in the plant life when the wild samples were assayed. Plant age, the part of the plant from which the uterotonic principle is extracted, climate, altitude, and soil constituents are other possible influences on uterotonic potency. A sample of the zoapatle aqueous crude extract with the highest uterotonic potency will be assayed for its luteolytic activity in an animal model.