Inhibition of P-glycoprotein function by procyanidine on blood-brain barrier.
Phytother Res
; 23(7): 933-7, 2009 Jul.
Article
em En
| MEDLINE
| ID: mdl-19172664
ABSTRACT
The inhibitory effects of procyanidine, one of the components from the bark of Pinus massoniana Lamb, on the P-glycoprotein (P-gp) function of the blood-brain barrier (BBB) were studied using in vitro rat brain microvessel endothelial cells (RBMECs) and nude mice transplanted with human cerebroma. Quantitative accumulation and efflux of rhodamine 123 (Rh123), a P-gp substrate, were determined using a fluorescence spectrophotometer as a measure of P-gp function. Procyanidine markedly increased the accumulation of Rh123 by inhibiting its efflux in a dose-dependent manner. A 5-fold increase in cellular Rh123 was observed for procyanidine at 10 micromol/L. The verapamil-stimulated ATPase activity in plasma membrane vesicles from the RBMECs was estimated by measuring inorganic phosphate liberation. Procyanidine significantly inhibited the verapamil-induced P-gp ATPase activity by 78% when pretreated with 10 micromol/L in a concentration-dependent manner. The inhibition of P-gp by procyanidine was suggested to be at least partly due to its inhibition of P-gp ATPase. Procyanidine markedly improved the therapeutic effects of adriamycin (ADM) on nude mice transplanted with human cerebroma, compared with solitary treatment of ADM. The combination of 80 mg/kg procyanidine with 2 mg/kg ADM significantly elevated the days of survival with an increase in life span of 76%. The findings suggested that procyanidine was a potent inhibitor of P-gp on BBB and could improve the therapeutic effects on cerebral tumors of some drugs which are difficult to accumulate in the brain.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
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Barreira Hematoencefálica
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Catequina
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Biflavonoides
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Proantocianidinas
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article