Interaction of deoxyschizandrin and schizandrin B with liver uptake transporters OATP1B1 and OATP1B3

Abstract

1. Deoxyschizandrin and schizandrin B have diverse pharmacological effects, including hepatoprotective activity. We aim to study their hepatic uptake and their effects on the hepatic uptake of other clinical drugs mediated by OATP1B1 and OATP1B3.

2. Deoxyschizandrin exhibited a high affinity for OATP1B1 with K_m of 17.61 ± 0.43 μM but a low affinity for OATP1B3. Similarly, schizandrin B also showed a strong affinity for OATP1B1 with K_m of 18.45 ± 1.23 μM but a weak affinity for OATP1B3.

3. Atorvastatin and rifampicin could inhibit the uptake of deoxyschizandrin and schizandrin B mediated by OATP1B1.

4. Intriguingly, both deoxyschizandrin and schizandrin B significantly promoted the uptake of atorvastatin (with EC₅₀ of 50.58 ± 8.08 and 24.70 ± 5.82 µM, respectively) and rosuvastatin (with EC₅₀ of 13.46 ± 2.70 and 8.99 ± 4.73 µM, respectively) mediated by OATP1B1. Deoxyschizandrin could markedly promote the uptake of fluvastatin but inhibit the uptake of sodium taurocholate (TCNa) mediated by OATP1B1.

5. The promotion on hepatic uptake of statins mediated by OATP1B1 might lead to enhanced efficacy of cholesterol lowering and reduced risk of myopathy for hyperlipidemia patients when given statins together with deoxyschizandrin or schizandrin B.

Keywords:

• Deoxyschizandrin
• schizandrin B
• OATPs
• interactions

Disclosure statement

None of the authors have any conflicts of interest with respect to this paper.

Additional information

Funding

This work was supported by National Natural Science Fund [81760672, 81160411, 81560606], Jiangxi Provincial Natural Science Fund [20151BAB205084], and China National Fund Organization.