期刊
PHYTOTHERAPY RESEARCH
卷 23, 期 7, 页码 933-937出版社
WILEY
DOI: 10.1002/ptr.2781
关键词
P-glycoprotein; blood-brain barrier; procyanidine; cerebral tumor
资金
- National Natural Science Foundation of China [30771690]
- China Postdoctoral Science Foundation [20070410343]
- Jiangsu Planned Projects for Postdoctoral Research Funds [0601050B]
- The Drug Efficacy Study and Evaluation Service Center of Jiangsu Province [BM2005103]
- Specific fund for public interest research of traditional chinese medicine, Ministry of finance [200707008]
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 mu mol/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 mu mol/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. Copyright (C) 2009 John Wiley & Sons, Ltd.
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