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Interaction of Deoxyschizandrin and Schizandrin B With Liver Uptake Transporters OATP1B1 and OATP1B3

Interaction of Deoxyschizandrin and Schizandrin B With Liver Uptake Transporters OATP1B1 and OATP1B3

Yanli Lu, Qingqing Hu, Lin Chen, Hong Zhang, Shibo Huang, Yuqing Xiong, Chunhua Xia

Xenobiotica. 2019 Feb;49(2):239-246.

PMID: 29405807

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 Km of 17.61 ± 0.43 μM but a low affinity for OATP1B3. Similarly, schizandrin B also showed a strong affinity for OATP1B1 with Km 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP61281376	Schizandrin B		61281-37-6	Price

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