核桃仁对补骨脂在大鼠体内的药代动力学影响

Effects of walnut kernel on the pharmacokinetics of psoralea corylifolia in rats

关键词:  补骨脂  核桃仁  药代动力学  超高效液相色谱-串联质谱联用技术

Key words:  psoralea corylifolia  walnut kernel  pharmacokinetics  UHPLC-MS/MS

摘要:

[目的] 实验旨在研究核桃仁对补骨脂在大鼠体内的药代动力学影响。[方法] 12只雄性SD大鼠分为补骨脂组（补骨脂：1.05 g/kg）和配伍给药组（补骨脂：1.05 g/kg；核桃仁：0.66 g/kg），每组6只。在给药前（0 h）和给药后12个时间点眼眶静脉取血约300 μL，取上层血浆，用所建立的分析方法检测。[结果] 药代动力学参数结果显示，配伍组大鼠体内的多数成分出现血浆浓度-时间曲线下面积（AUC）和药峰浓度（C_max）值水平降低现象，包括异补骨脂素、补骨脂二氢黄酮甲醚、异补骨脂二氢黄酮、新补骨脂异黄酮和巴库查尔酮。[结论] 研究表明核桃仁可通过降低补骨脂多数活性成分的体内暴露水平，同时降低各成分在大鼠体内的滞留时间，影响补骨脂在大鼠体内的药代动力学行为，从药代动力学角度阐释核桃仁减轻补骨脂所致肝毒性的可能机制。

Abstract:

[Objective] This experiment aimed to investigate the effect of walnut kernel on the pharmacokinetics of Psoralea corylifolia extract in rats. [Methods] Twelve male SD rats were divided into two groups（n=6 per group）：the Psoralea corylifolia group（receiving Psoralea corylifolia extract at 1.05 g/kg） and the co-administration group （receiving Psoralea corylifolia extract at 1.05 g/kg plus walnut kernel at 0.66 g/kg）. Approximately 300 μL of blood was collected from the orbital venous plexus before administration（0 h） and at 12 time points post-administration. The upper plasma layer was collected and analyzed using the established method. [Results] The pharmacokinetic parameters showed that the most of the compatible rats had decreased AUC and Cmax levels, including isopsoralen, bavachinin, isobavachalcone, neobavaisoflavone and bakuchalcone. [Conclusion] This study indicates that walnut kernel can reduce the systemic exposure levels and shorten the retention time of most active components of Psoralea corylifolia in rats, thereby altering its pharmacokinetic profile. This finding provides a pharmacokinetic perspective on the potential mechanism by which walnut kernel alleviates Psoralea corylifolia-induced hepatotoxicity.