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圣约翰草提取物含有高的超蛋白,不会诱导人体血脑屏障中的P-糖蛋白活性
Myriam El Biali1,2, Michael Wölfl-Duchek1,3, Matthias Jackwerth1
1Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
圣约翰草 (SJW) 不会诱导人体血脑屏障 (BBB) 的P-糖蛋白 (P-gp). 这种草药会影响外围P-gp和CYP酶,但不会通过BBB通过中枢神经系统药物暴露.
科学领域:
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
- 草药研究 草药研究
背景情况:
- 圣约翰草 (SJW) 是一种众所周知的抗抑郁作用的草药.
- 已知SJW是肠道和肝脏P450 (CYP) 酶和P-糖蛋白 (P-gp) 的诱导剂.
- 通过SJW在血脑屏障 (BBB) 上可能诱导P-gp,可能会影响中枢神经系统 (CNS) 药物疗效.
研究的目的:
- 调查SJW对人类BBB的P-gp活性的影响.
- 评估SJW对外周P-gp和CYP酶活性的影响.
- 为了确定SJW是否影响中枢神经系统向药物的脑部暴露.
主要方法:
- 使用[11C]美托克洛普拉米德的正子发射断层扫描 (PET) 成像来评估BBB P-gp活性.
- 采用尾酒表型方法 (咖啡因,奥梅普拉,德克斯特罗梅索芬,米达佐/费克索芬阿丁) 来评估外围P-gp和CYP活性.
- 给12-19天的健康志愿者 (n=10) 服用SJW提取物 (1800毫克/天).
主要成果:
- SJW显著增加了外围P-gp,CYP3A和CYP2C19活动.
- 没有观察到大脑分布或BBB P-gp介导的[11C]metoclopramide流动中的显著变化.
- 与BBB运输有关的P-gp基质的外周代谢没有显著改变.
结论:
- SJW 提取物不会显著诱导人类血脑屏障中的 P-gp 活性.
- 尽管诱导了外周P-gp和CYPs,但SJW不太可能在BBB中引起中枢神经系统药物的P-gp介导药物相互作用.
- 在BBB中不预计涉及SJW和中枢神经系统向的P-gp基质的临床相关药物相互作用.
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