PDF(Pubmed)
Abstract：
Hydroxy-α-sanshool (HAS) is the predominant active compound in Zanthoxylum bungeanum Maxim (ZBM). Our present work was aimed to explore the in vitro metabolism characteristics, and in vivo pharmacokinetic (PK) profile of HAS. Plasma (human), liver microsomes, and hepatocytes (human, monkey, dog, mouse, and rat) were collected for HAS metabolism studies in vitro and HAS elimination rates in liver microsomes and hepatocytes of different species were investigated. In addition, five recombinant human CYP enzymes were used to identify CYP isoforms of HAS. Finally, the PK properties of HAS in rats in vivo were studied by oral administration (p.o.). The results showed that HAS stably metabolized in human and rat liver microsomes and human hepatocytes, and the binding of HAS to human plasma proteins was nonspecific; HAS has strong inhibitory effects on CYP2C9 and CYP2D6 of human liver microsomes. In addition, in vivo PK study, HAS is rapidly absorbed in rats after oral administration. In conclusion, the in vivo and in vitro metabolic studies of HAS in this study provide data support for its further development and application, and the metabolic profiles of different species can be used as a reference for its safety evaluation.
摘要：
羟基-α-sanshool（HAS）是花椒（ZBM）中的主要活性化合物。我们目前的工作旨在探索体外代谢特征，和HAS的体内药代动力学(PK)概况。血浆（人），肝微粒体,和肝细胞（人类，猴子,狗,鼠标,和大鼠）被收集用于体外HAS代谢研究，并研究了不同物种的肝微粒体和肝细胞中的HAS消除率。此外,使用五种重组人CYP酶鉴定HAS的CYP亚型。最后,通过口服给药(p.o.)研究了HAS在大鼠体内的PK特性。结果表明，HAS在人和大鼠肝微粒体和人肝细胞中稳定代谢，HAS与人血浆蛋白的结合是非特异性的；HAS对人肝微粒体的CYP2C9和CYP2D6具有很强的抑制作用。此外,体内PK研究，口服后，HAS在大鼠中迅速吸收。总之,本研究中HAS的体内外代谢研究为其进一步开发和应用提供了数据支持,不同物种的代谢谱可作为其安全性评价的参考。
