In vitro to in vivo evidence of the inhibitor characteristics of Schisandra lignans toward P-glycoprotein.

Abstract Concomitant administration of herbal medicines with drugs that are P-glycoprotein (P-gp) substrates may produce significant herb–drug interactions. The purpose of this study was to evaluate the effects of Schisandra lignans extract (SLE) on P-gp thoroughly in vitro and in vivo , and to investigate the possible P-gp-based herb–drug interactions. In the in vitro experiments, the effect of SLE on the uptake and transport for P-gp substrates in Caco-2, LLC-PK1 and L-MDR1 cells were carefully investigated. Verapamil, a known P-gp inhibitor, was used as a positive control drug. Results shown that, 10 μM verapamil and SLE (0.5, 2.0, and 10.0 μg/ml) were observed to significantly enhance the uptake and inhibit the efflux ratio of P-gp substrates in Caco-2 and L-MDR1 cells. In vivo experiments showed that single-dose SLE at 500 mg/kg could increase the area under the plasma concentration time curve of digoxin and vincrisine significantly without affecting terminal elimination half-time. Long-term treatment with SLE for continuous 10 days could also increase the absorption of P-gp substrates with greatly down regulation of P-gp expression in rat intestinal and brain tissues. In conclusion, SLE was a strong P-gp inhibitor, which indicated a potential herb–drug interaction when SLE was co-administered with P-gp substrate drugs.