新獐牙菜苦苷 B 通过抑制 MRP2 和 BCRP 增加了獐牙菜苦苷在川西獐牙菜中的生物利用度。
Neochamaejasmin B increases the bioavailability of chamaechromone coexisting in Stellera chamaejasme L. via inhibition of MRP2 and BCRP.
机构信息
Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China; Laboratory of Natural Medicine, School of Forestry and Bio-technology, Zhejiang A&F University, Lin'an 311300, China.
Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
出版信息
Int J Pharm. 2015 Dec 30;496(2):440-7. doi: 10.1016/j.ijpharm.2015.10.038. Epub 2015 Oct 26.
Chamaechromone and neochamaejasmin B (NCB) are the most abundant components in the dried roots of the toxic perennial herb Stellera chamaejasme L. and have pharmacological activities. The objective of this study was to investigate the transport mechanism of these two components in vivo and in vitro. The transport and cellular accumulation studies in Madin-Darby canine kidney (MDCK) cells overexpressing human multidrug resistance protein 2 (MRP2) or P-gp and LLC-PK1 cells overexpressing human breast cancer resistance protein (BCRP) were performed. The results showed that chamaechromone was a good substrate of MRP2 and BCRP but not a substrate of P-gp. NCB was found to be a MRP2 inhibitor in transfected cells and significantly enhanced the cellular accumulation of chamaechromone in MDCK cells overexpressing MRP2. Similar results were obtained in LLC-PK1-BCRP cells. In addition, the influence of NCB on the bioavailability of chamaechromone following their co-administration was also determined in rats. The results showed that the area under the plasma concentration-time curve and maximal plasma concentration of chamaechromone in rats were increased by 48.9% and 81.9%, respectively. The mechanism of improving the oral bioavailability of chamaechromone was attributable to the inhibition of the BCRP and MRP2-mediated efflux of chamaechromone by NCB.
喇叭茶酮和新蛇麻素 B（NCB）是瑞香科狼毒属多年生有毒植物狼毒根干中的最主要成分，具有药理学活性。本研究旨在探讨这两种成分在体内和体外的转运机制。在过表达人多药耐药蛋白 2（MRP2）的 Madin-Darby 犬肾（MDCK）细胞和过表达人乳腺癌耐药蛋白（BCRP）的 LLC-PK1 细胞中进行了这两种成分的转运和细胞内蓄积研究。结果表明，喇叭茶酮是 MRP2 和 BCRP 的良好底物，但不是 P-糖蛋白的底物。NCB 被发现是转染细胞中 MRP2 的抑制剂，并显著增加了过表达 MRP2 的 MDCK 细胞中喇叭茶酮的细胞内蓄积。在 LLC-PK1-BCRP 细胞中也获得了类似的结果。此外，还在大鼠中确定了 NCB 对喇叭茶酮生物利用度的影响。结果表明，喇叭茶酮在大鼠体内的血浆浓度-时间曲线下面积和最大血浆浓度分别增加了 48.9%和 81.9%。NCB 提高喇叭茶酮口服生物利用度的机制归因于 NCB 抑制了 BCRP 和 MRP2 介导的喇叭茶酮外排。
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