Inhibition of P‐glycoprotein function by procyanidine on blood–brain barrier

This is the authors' abstract. We don't add key points for this paper.

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.