RESUMEN
Four prenylated flavanones were isolated from the methanol extract of the flowers of Azadirachta indica (the neem tree) as potent antimutagens against Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) in the Salmonella typhimurium TA98 assay by activity-guided fractionation. Spectroscopic properties revealed that those compounds were 5,7,4'-trihydroxy-8-prenylflavanone (1), 5,4'-dihydroxy-7-methoxy-8-prenylflavanone (2), 5,7,4'-trihydroxy-3',8-diprenylflavanone (3), and 5,7,4'-trihydroxy-3',5'-diprenylflavanone (4). All isolated compounds were found for the first time in this plant. The antimutagenic IC(50) values of compounds 1-4 were 2.7 +/- 0.1, 3.7 +/- 0.1, 11.1 +/- 0.1, and 18.6 +/- 0.1 microM in the preincubation mixture, respectively. These compounds also similarly inhibited the mutagenicity of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). All of the compounds 1-4 strongly inhibited ethoxyresorufin O-dealkylation activity of cytochrome P450 1A isoforms, which catalyze N-hydroxylation of heterocyclic amines. However, compounds 1-4 did not show significant inhibition against the direct-acting mutagen NaN(3). Thus, the antimutagenic effect of compounds 1-4 would be mainly based on the inhibition of the enzymatic activation of heterocyclic amines.
Asunto(s)
Antimutagênicos/aislamiento & purificación , Azadirachta/química , Flavanonas/aislamiento & purificación , Flores/química , Compuestos Heterocíclicos/antagonistas & inhibidores , Animales , Carbolinas/antagonistas & inhibidores , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Furilfuramida/farmacología , Hígado/enzimología , Espectroscopía de Resonancia Magnética , Masculino , Metanol , Mutágenos/farmacología , Nitrógeno/antagonistas & inhibidores , Extractos Vegetales/farmacología , Prenilación de Proteína , Ratas , Ratas Sprague-DawleyRESUMEN
There is growing public interest in traditional medicine. PADMA 28, a multicompound herbal preparation derived from Tibetan medicine, has proven efficacy in some clinical trials and tests at the cellular level. We report here on studies of PADMA 28 at the molecular level. Extracts of PADMA 28 contain both reducing and metal ion-chelating substances. In this way, PADMA 28 acts as a powerful antioxidant or prooxidant, depending on its concentration and the reaction under study.
Asunto(s)
Antioxidantes/química , Oxidantes/química , Extractos Vegetales/química , Plantas Medicinales/química , Antioxidantes/metabolismo , Grupo Citocromo c/metabolismo , Daño del ADN/efectos de los fármacos , Compuestos Férricos/metabolismo , Compuestos Ferrosos/metabolismo , Peroxidasa de Rábano Silvestre/metabolismo , Quelantes del Hierro/química , Medicina Tradicional de Asia Oriental , Nitrógeno/antagonistas & inhibidores , Nitrógeno/metabolismo , Oxidantes/metabolismo , Oxidación-Reducción , Extractos Vegetales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sustancias Reductoras/química , Especificidad por SustratoRESUMEN
The nitrification inhibition (NI) bioassay guided fractionation of the methanol extract of lyophilized and milled roots of Leuceana leucocephala resulted in the isolation of four compounds, 1-4, as confirmed from their 1H and 13C NMR spectral data. Compound 1, gallocatechin, was the most active NI inhibitor at 12 microg/mL. Epigallocatechin, 2, and epicatechin, 4, isolated as mixtures, were not assayed individually for their NI inhibitory activities against the nitrification bacterium Nitrosomonas europaea.
Asunto(s)
Fabaceae/química , Nitrógeno/antagonistas & inhibidores , Nitrosomonas/metabolismo , Plantas Medicinales , Catequina/análogos & derivados , Catequina/análisis , Espectroscopía de Resonancia Magnética , Nitrógeno/metabolismoRESUMEN
Dynamics of cardiac rhythm has been considered according to rhythmocardiographic characteristics of heart rate under orthostatic test and one-stage step-test in four altitude chamber experiments where air under pressure of 0.4-1.1 MPa is used as a breathing mixture. It is shown that these characteristics linearly depend on the partial nitrogen and oxygen pressure and hyperbaric bradycardia essentially decreases in the final period of isopression due to toxic oxygen effect. Cytochrome C decreases hyperbaric bradycardia. Under hyperbaric conditions the regulation of cardiac rhythm proceeds with altered central vegetative effects provided a direct effect of higher nitrogen and oxygen pressure on the sinusal node cells.