Effects of puerarin on the pharmacokinetics of astragaloside IV in rats and its potential mechanism
Effects of puerarin on the pharmacokinetics of astragaloside IV in rats and its potential mechanism
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DOI：
10.1080/13880209.2020.1746362
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发表时间：
2020-01-01
影响因子：
3.8
通讯作者：
Wang, Lili
中科院分区：
文献类型：
--
作者：
Zhang, Huan;Song, Jiaying;Wang, Lili
内容：葛根素和黄芪甲苷（AS-IV）在中国临床上有时一起用于治疗疾病，但葛根素和AS-IV之间的药物相互作用尚不清楚。目的：研究葛根素对黄芪甲苷在大鼠体内药代动力学的影响，阐明其主要作用机制。材料与方法：研究了Sprague-Dawley大鼠经口给予葛根苷IV（20 mg/kg）（有或无葛根素预处理（100 mg/kg/天，持续7天））的药代动力学特征。采用Caco-2细胞transwell模型和大鼠肝微粒体研究了葛根素对AS-IV转运和代谢稳定性的影响。结果如下：结果显示，葛根素可显著增加AS-IV的血浆峰浓度（从48.58 ± 7.26 ng/mL增加至72.71 ± 0.62 ng/mL），并降低口服清除率（从47.5 ± 8.91 L/h/kg减少至27.15 ± 9.27 L/h/kg）。Caco-2细胞transwell实验表明，葛根素可将黄芪甲苷IV的外排率从1.89降低至1.26，并且葛根素预处理降低了黄芪甲苷IV的固有清除率（34.8 +/- 2.9 vs. 41.5 +/- 3.8 μ L/min/mg蛋白）。讨论和结论：结果表明，葛根素可通过增加黄芪甲苷在大鼠体内的吸收或抑制其在大鼠体内的代谢，显著改变黄芪甲苷在大鼠体内的药代动力学。
Context: Puerarin and astragaloside IV (AS-IV) are sometimes used together for the treatment of disease in Chinese clinics, however, the drug-drug interaction between puerarin and AS-IV is still unknown. Objective: This study investigates the effects of puerarin on the pharmacokinetics of astragaloside IV in rats and clarifies its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of astragaloside IV (20 mg/kg) in Sprague-Dawley rats, with or without pre-treatment of puerarin (100 mg/kg/day for 7 days) were investigated. The effects of puerarin on the transport and metabolic stability of AS-IV were also investigated using Caco-2 cell transwell model and rat liver microsomes. Results: The results showed that puerarin could significantly increase the peak plasma concentration (from 48.58 +/- 7.26 to 72.71 +/- 0.62 ng/mL), and decrease the oral clearance (from 47.5 +/- 8.91 to 27.15 +/- 9.27 L/h/kg) of AS-IV. The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of astragaloside IV from 1.89 to 1.26, and the intrinsic clearance rate of astragaloside IV was decreased by the pre-treatment with puerarin (34.8 +/- 2.9 vs. 41.5 +/- 3.8 mu L/min/mg protein). Discussion and conclusions: These results indicated that puerarin could significantly change the pharmacokinetic profiles of astragaloside IV, via increasing the absorption of astragaloside IV or inhibiting the metabolism of astragaloside IV in rats.