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
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脱氧五味子素和五味子素 B 与肝摄取转运蛋白 OATP1B1 和 OATP1B3 的相互作用
DOI：
10.1080/00498254.2018.1437647
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发表时间：
2019-02
期刊：
影响因子：
1.8
通讯作者：
Xia Chunhua
中科院分区：
文献类型：
--
作者：
Lu Yanli;Hu Qingqing;Chen Lin;Zhang Hong;Huang Shibo;Xiong Yuqing;Xia Chunhua
摘要1.脱氧五味子醇甲和五味子醇甲B具有不同的药理作用，包括肝保护活性。我们的目的是研究其肝脏摄取及其对OATP 1B1和OATP 1B3介导的其他临床药物肝脏摄取的影响。2.脱氧野菊花苷对OATP 1B1表现出高亲和力，Km为17.61 ± 0.43 μM，但对OATP 1B3表现出低亲和力。同样，野牡丹苷B也显示出对OATP 1B1的强亲和力，Km为18.45 ± 1.23 μM，但对OATP 1B3的亲和力较弱。3.阿托伐他汀和利福平可抑制OATP 1B1介导的脱氧野牡丹苷和野牡丹苷B的摄取。4.有趣的是，脱氧野牡丹苷和野牡丹苷B均显著促进OATP 1B1介导的阿托伐他汀（EC50分别为50.58 ± 8.08和24.70 ± 5.82 µM）和瑞舒伐他汀（EC50分别为13.46 ± 2.70和8.99 ± 4.73 µM）的摄取。脱氧野百合素可显著促进OATP 1B1介导的氟伐他汀摄取，但抑制OATP 1B1介导的牛磺胆酸钠（TCNa）摄取。5.当他汀类药物与脱氧野山竹素或野山竹素B联合给药时，OATP 1B1介导的他汀类药物肝摄取的促进可能导致高脂血症患者降低胆固醇的疗效增强，并降低肌病的风险。
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.
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