RESUMEN
Baicalein (BA) is a flavonoid with wide-ranging pharmacological activity. However, its biological evaluation is hampered by its low solubility in aqueous medium, making forms of incorporation that improve its solubility necessary. In the present study, BA was combined with a solution of silk fibroin protein (SF), a biomaterial used too as a drug carrier, to evaluate the anti-inflammatory potential of this combination, in vivo, in an experimental model, zebrafish (Danio rerio). Baicalein-silk fibroin (BASF) improved the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging rate (95%) in comparison with BA in solution. The acute toxicity study and histopathological analysis in zebrafish showed that BASF has low cytotoxic potential, except for the maxim dose of 2000 mg/kg. The use of BA in combination with SF enhanced the anti-inflammatory effect of flavonoids by inducing inflammatory peritoneal edema through carrageenan and achieved 77.6% inhibition of abdominal edema at a dose of 75 mg/kg. The results showed that the BASF, significantly increases the bioavailability and therapeutic effect of flavonoids and several results observed in this study may help in the development of new drugs.
Asunto(s)
Fibroínas , Animales , Fibroínas/farmacología , Pez Cebra , Flavonoides , Antiinflamatorios/farmacología , Edema/inducido químicamente , Edema/tratamiento farmacológico , SedaRESUMEN
The effects of the Securinega alkaloid (+)-phyllanthidine on Leishmania (L.) amazonensis and the first chemical investigation of Margaritaria nobilis L.f. (Phyllanthaceae) are described. Treating the parasites with this alkaloid caused a dose-dependent reduction in promastigote growth of 67.68% (IC50 82.37 µg/mL or 353 µM) and in amastigote growth of 83.96% (IC50 49.11 µg/mL or 210 µM), together with ultrastructural alterations in the promastigotes. No cytotoxic effect was detected in mammalian cells (CC50 1727.48 µg/mL or CC50 5268 µM). Classical chromatographic techniques and spectral methods led to the isolation and identification of betulinic acid, kaempferol, corilagin, gallic acid and its methyl ester, besides (+)-phyllanthidine from M. nobilis leaves and stems. Margaritaria nobilis is another source of the small group of Securinega alkaloids, together with other Phyllanthaceae (Euphorbiaceae s.l.) species. The low toxicity to macrophages and the effects against promastigotes and amastigotes are suggestive that (+)-phyllanthidine could be a promising antileishmanial agent for treating cutaneous leishmaniasis.
Asunto(s)
Antiprotozoarios/farmacología , Euphorbiaceae/química , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Leishmania braziliensis/efectos de los fármacos , Estadios del Ciclo de Vida/efectos de los fármacos , Fitoquímicos/farmacología , Alcaloides/aislamiento & purificación , Animales , Antiprotozoarios/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ácido Gálico/aislamiento & purificación , Glucósidos/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Taninos Hidrolizables/aislamiento & purificación , Concentración 50 Inhibidora , Quempferoles/aislamiento & purificación , Leishmania braziliensis/crecimiento & desarrollo , Leishmania braziliensis/ultraestructura , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Triterpenos Pentacíclicos , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/química , Cultivo Primario de Células , Triterpenos/aislamiento & purificación , Ácido BetulínicoRESUMEN
The chemical study of Eugenia protenta McVaugh extracts performed by classical and high-performance liquid chromatography techniques and spectral methods has led to the identification of known triterpenoids, flavonoids and an acetophenone derivative (dimethylxanthoxylin). The effect of dimethylxanthoxylin on Leishmania (Leishmania) amazonensis was evaluated against the promastigotes forms after 96 h of treatment. Dimethylxanthoxylin reduced 57 and 59% of the promastigotes growth when treated with 50 and 100 µg/mL solutions, respectively (IC50 117.35 µg/mL or 52.3 µM). Cytotoxicity experiments using MTT assays showed that this substance did not promote cell death after 24 h of treatment. Dimethylxanthoxylin was active on the promastigotes and could be a promising agent for treating leishmaniasis.