Chen Lin, Liao Lu, Zhai Ting, Huang Xiangtao, Chen Yong
Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan, 430062, China.
School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Eur J Drug Metab Pharmacokinet. 2019 Feb;44(1):103-109. doi: 10.1007/s13318-018-0499-1.
Borneol, a traditional Chinese medicine (TCM), is often orally co-administered with other TCM and chemical drugs, but the drug-drug interactions between borneol and the other compounds remains unclear. This work investigates the effect of orally administered borneol on the transcription and expression of hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) in rats, aiming to obtain essential information to guide its clinical applications.
Rats were administered borneol (33, 100 and 300 mg/kg/day, respectively) and vehicle (control) orally via intragastric gavage for 7 consecutive days. The mRNA levels of rat hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) were determined using real-time quantitative PCR, while the hepatic Ntcp, Mdrla, Mrp2, Mrp4 and Mrp5 proteins were quantified using western blotting.
The oral administration of borneol led to dose-dependent inhibition of mRNA and protein expression of Mrp4 and Mdr1a, dose-independent inhibition of mRNA and protein expression of Mrp2, and inverse dose-dependent inhibition of mRNA and protein expression of Ntcp. No significant effects were observed for mRNA expression of the other transporters tested following borneol administration.
Oral administration of borneol may affect the metabolism of substances that are involved in bile acid enterohepatic circulation and substrates of Ntcp, Mdrla, Mrp2 and Mrp4 transporters.
冰片作为一种中药，常与其他中药及化学药物联合口服给药，但冰片与其他化合物之间的药物相互作用尚不清楚。本研究旨在探讨口服冰片对大鼠肝脏摄取转运体（Ntcp、Oatp2b1、Oatp1a1、Oatp1a4、Oct1、Oct2、Octn2和Oat2）及外排转运体（Mdrla、Mrp2、Mrp4和Mrp5）转录和表达的影响，以期获得指导其临床应用的重要信息。
将大鼠分别给予冰片（分别为33、100和300mg/kg/天）和赋形剂（对照组），连续7天经口灌胃。采用实时定量PCR法检测大鼠肝脏摄取转运体（Ntcp、Oatp2b1、Oatp1a1、Oatp1a4、Oct1、Oct2、Octn2和Oat2）及外排转运体（Mdrla、Mrp2、Mrp4和Mrp5）的mRNA水平，同时采用蛋白质免疫印迹法对肝脏Ntcp、Mdrla、Mrp2、Mrp4和Mrp5蛋白进行定量分析。
口服冰片导致Mrp4和Mdr1a的mRNA和蛋白表达呈剂量依赖性抑制，Mrp2的mRNA和蛋白表达呈非剂量依赖性抑制，Ntcp的mRNA和蛋白表达呈剂量依赖性反向抑制。冰片给药后，未观察到其他所检测转运体的mRNA表达有显著影响。
口服冰片可能影响参与胆汁酸肠肝循环的物质以及Ntcp、Mdrla、Mrp2和Mrp4转运体底物的代谢。
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