RESUMO
CONTEXT: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations. OBJECTIVE: Phytochemical investigation of D. glabra leaves and its protective potential against CCl4 inducing changes in the genetic materials. MATERIALS AND METHODS: D. glabra extract, DGE (70% MeOH/H2O), was applied to polyamide column chromatography, eluting with MeOH/H2O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds. Three DGE doses (50, 100 and 200 mg/kg bw/d) were administrated for 8 weeks intragastrically to male albino rats prior treated with CCl4 (0.5 mL/kg/bw). The reactive oxygen species (ROS) levels, expression changes of glutamate transporters (GLAST, GLT-1 and SNAT3) mRNA, DNA fragmentation and glutathione peroxidase (GPx) activity were investigated in the liver tissues of these rats. RESULTS: Isorhamnetin-3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside, isorhamnetin-3-O-α-rhamnopyranoside-7-O-ß-glucopyranoside, kaempferol-3,7-di-O-α-rhamnopyranoside, isorhamnetin-3-O-ß-glucopyranoside, kaempferol-3-O-ß-glucopyranoside, isorhamnetin and kaempferol were identified. DGE (200 mg/kg bw) + CCl4 exhibited the most significant reduction in ROS levels and DNA fragmentation with 251.3% and141% compared to 523.1% and 273.2% for CCl4, respectively. Additionally, it increased significantly the mRNA expression of GLAST, GLT-1 and SNAT3 to 2.16-, 1.72- and 2.09-fold, respectively. Also, GPx activity was increased to 4.8 U/mg protein/min compared to CCl4 (1.8 U/mg protein/min). DISCUSSION AND CONCLUSION: Flavonoid constituents, antioxidant effect and genotoxic protection activity of D. glabra were first reported. DGE may be valuable in the treatment and hindrance of hepatic oxidative stress and genotoxicity.
Assuntos
Antioxidantes/farmacologia , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Flavonoides/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Salvadoraceae/química , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Animais , Antioxidantes/isolamento & purificação , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Transportador 1 de Aminoácido Excitatório/genética , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Transportador 2 de Aminoácido Excitatório/metabolismo , Flavonoides/isolamento & purificação , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Masculino , Metanol/química , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Solventes/química , Regulação para CimaRESUMO
Bioactivity-guided fractionation of an ethanolic extract of Vitis repens led to the isolation of resveratrol (1), 11-O-acetyl bergenin (2), and stigmast-4-en-3-one (3). The compounds were examined for their in vitro antitrypanosomal activities against trypomastigotes of Trypanosoma evansi. Resveratrol showed antitrypanosomal activity with an IC50 value of 0.13 microM, whereas 11-O-acetyl bergenin and stigmast-4-en-3-one exhibited IC50 values of 0.17 and 0.15 microM, respectively.
Assuntos
Extratos Vegetais/análise , Plantas Medicinais/química , Tripanossomicidas/isolamento & purificação , Vitis/química , Mianmar , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacosRESUMO
The crude extract of Brucea javanica showed strong in vitro inhibitory activity against Trypanosoma evansi. Among the isolated quassinoids, bruceines A, C, and bruceantinol were found to be the most potent compounds against T. evansi. To gain a deeper understanding of the relationship between the free hydroxyl groups and the activity, several O-acetylated derivatives of bruceines A and C were synthesized and their in vitro antitrypanosomal activities against trypomastigotes of T. evansi were examined and compared with those of the original compounds. The following structure-activity relationships were observed: (1) the free hydroxyl groups at positions C-3, C-11, and C-12 are essential for antitrypanosomal activity; (2) the C-11 and C-12 hydroxyl groups are more important for the activity than the enolic hydroxyl group at C-3, and; (3) the free hydroxyl group at C-4' of bruceine C does not have any significant effect on the activity.
Assuntos
Quassinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Acetilação , Brucea/química , Frutas , Estrutura Molecular , Quassinas/química , Quassinas/isolamento & purificação , Relação Estrutura-Atividade , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificaçãoRESUMO
We have previously reported a tetraketide origin for theobroxide and its related compound. In the present study, bioconversion of natural and deuterium-labeled precursors of this proposed biosynthetic pathway by Lasiodipoldia theobromae was investigated. Theobroxide was quantified after bioconversion from each proposed precursor. The transformation of the isotopically labeled precursor to products was tracked by 2H NMR measurement.
Assuntos
Ascomicetos/metabolismo , Cicloexanos/metabolismo , Compostos de Epóxi/metabolismo , Biotransformação , Deutério , Espectroscopia de Ressonância MagnéticaRESUMO
The medicinal plant Brucea javanica (L.) Merr. (Simaroubaceae) is widely distributed throughout Asia where its bitter fruits have been used in traditional medicine for various ailments. Fifteen C-20 quassinoids were isolated from the fruits of B. javanica and examined for their in vitro antitrypanosomal activities against trypomastigotes of Trypanosoma evansi. Bruceine A, bruceantinol, bruceine C, brusatol, and bruceine B showed strong antitrypanosomal activities with IC(50) values in the range of 2.9-17.8nM, which compared well with the standard trypanocidal drugs diminazene aceturate (IC(50)=8.8nM) and suramin (IC(50)=43.2nM). However, dehydrobruceine A, dehydrobruceine B, and dehydrobrusatol were about 2100, 900, and 1200 times less active, respectively, than bruceine A, bruceine B, and brusatol. The relationship of the structure and antitrypanosomal activity of these quassinoid compounds suggested that the presence of a diosphenol moiety in ring A and the nature of the C-15 side chain are important for their activities against T. evansi. This is the first report on the antitrypanosomal activity of isolated quassinoids.