Effect of six bioactive lignans of Wuzhi tablet (Schisandra sphenanthera extract) on P-glycoprotein and its herb-drug interaction with digoxin
10.16438/j.0513-4870.2018-0429
- VernacularTitle:6个五酯片木脂素活性成分对P-gp活性的影响及与地高辛的相互作用
- Author:
Xiao-ling QIN
1
;
Wen-hai DUAN
1
;
Ying WANG
2
;
Xiao CHEN
3
;
Min HUANG
4
;
Hui-chang BI
4
Author Information
1. Guangdong Food and Drug Vocational College, Guangzhou 510520, China
2. Department of Pharmacy, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
3. Department of Pharmacy, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
4. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
Wuzhi tablet;
Schisandra lignan;
digoxin;
pharmacokinetics;
P-gp;
Caco-2 cell
- From:
Acta Pharmaceutica Sinica
2018;53(8):1337-1343
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the effects of six Schisandra lignans of Wuzhi tablet (WZ, a preparation of ethanol extract of Schisandra sphenanthera) on the pharmacokinetic process of digoxin (DG, a classical P-gp substrate) after intravenous and oral administration in rats. The effect of Schisandra lignans on the transportion of DG in Caco-2 cells was further elucidated. Our data showed that the plasma concentrations of DG were increased to different extent following co-administration of schisandrin A, schisandrin B, schisandrol B and schisantherin A, respectively. Schisandrol B showed the most potent effect among the six lignans. However, schisandrin C and schisandrol A showed little effect on pharmacokinetic of DG. Schisandrol B led to 99.0% (P < 0.05) and 109.2% (P < 0.05) increase in the AUC after orally or intravenously administered of DG, suggesting that co-administration of schisandrol B induced a more potent effect on increasing hepatic bioavailability of DG than that of intestinal. Furthermore, in vitro transport experiment showed that schisandrin A, schisandrin B, schisandrol B and schisantherin A inhibited P-gp-mediated efflux of DG, suggested that these lignans inhibited the P-gp-mediated efflux of DG. In conclusion, the exposure of DG in rats was increased when co-administered with Schisandra lignans, and schisandrol B showed the strongest effect. The dramatic increase in oral bioavailability of digoxin in the presence of schisandrol B may be due to the inhibition of hepatic/renal P-gp activity.
