Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines

Abstract

Purpose: This study aims to investigate the potential of Oregon grape root extracts to modulate the activity of P-glycoprotein.Methods: We performed 3H-CsA or 3H-digoxin transport experiments in the absence or presence of two sources of Oregon grape root extracts (E1 and E2), berberine or berbamine in Caco-2 and MDCKII-MDR1 cells. In addition, real time quantitative polymerase chain reaction (RT-PCR) was performed in Caco-2 and LS-180 cells to investigate the mechanism of modulating P-glycoprotein.Results: Our results showed that in Caco-2 cells, Oregon grape root extracts (E1 and E2) (0.1–1 mg/mL) inhibited the efflux of CsA and digoxin in a dose-dependent manner. However, 0.05 mg/mL E1 significantly increased the absorption of digoxin. Ten µM berberine and 30 µM berbamine significantly reduced the efflux of CsA, while no measurable effect of berberine was observed with digoxin. In the MDCKII-MDR1 cells, 10 µM berberine and 30 µM berbamine inhibited the efflux of CsA and digoxin. Lastly, in real time RT-PCR study, Oregon grape root extract (0.1 mg/mL) up-regulated mRNA levels of human MDR1 in Caco-2 and LS-180 cells at 24 h.Conclusion: Our study showed that Oregon grape root extracts modulated P-glycoprotein, thereby may affect the bioavailability of drugs that are substrates of P-glycoprotein.

Lipid-lowering effect and oral transport characteristics study of curculigoside

“…Several transporter inhibitors to determine the transport characteristics of curculigoside: Verapamil (100 μM) was used to inhibit the efflux of P-glycoprotein (P-gp) ( 22 ); indomethacin (200 μM), MK 571(100 μM) and benzbromarone (50 μM) were used as multi-drug resistance associate protein (MRPs) inhibitors ( 22 – 25 ); Apigenin (25 μM) was used to inhibit the efflux of breast cancer resistance protein (BCRP); cimetidine (50 μM) and Sodium vanadate (50 μM) were used on Na/K-ATP ase and organic anion transporter (OAT) respectively ( 26 , 27 ). Before taking Samples, the inhibitors were added on the A and the B, and preincubated the monolayers at 37 °C for 15 min.…”