Sun Yao, Yao Tong, Li Hui, Peng Ying, Zheng Jiang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, People's Republic of China.
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, People's Republic of China.
J Biochem Mol Toxicol. 2017 Apr;31(4). doi: 10.1002/jbt.21876. Epub 2016 Nov 30.
Berbamine (BBM) is a bisbenzylisoquinoline alkaloid isolated from herbal medicine Berberis amurensis. BBM has been widely used for the treatment of leukemia. Recent studies demonstrated that exposure to BBM can give rise to cytotoxicity. The major objective of this study was to explore the metabolic activation of BBM in vitro and in vivo. Two oxidative metabolites (M1 and M2) and an N-acetylcysteine (NAC) conjugate (M3) were detected in human liver microsomal incubations of BBM supplemented with NAC, and the formation of all metabolites was NADPH dependent. Microsomal inhibition and recombinant P450 enzyme incubation studies demonstrated that P450 3A4 was the major enzyme responsible for the metabolic activation of BBM. In addition, a BBM-cysteine conjugate (M4) was detected in the urine of rats given BBM. The metabolism study will facilitate the understanding of the biochemical mechanisms of BBM-induced cytotoxicity.
小檗胺（BBM）是一种从草药黄柏中分离出的双苄基异喹啉生物碱。BBM已被广泛用于治疗白血病。最近的研究表明，接触BBM会产生细胞毒性。本研究的主要目的是探索BBM在体外和体内的代谢活化情况。在添加了N-乙酰半胱氨酸（NAC）的BBM人肝微粒体孵育中检测到两种氧化代谢物（M1和M2）和一种NAC缀合物（M3），所有代谢物的形成均依赖于NADPH。微粒体抑制和重组P450酶孵育研究表明，P450 3A4是负责BBM代谢活化的主要酶。此外，在给予BBM的大鼠尿液中检测到一种BBM-半胱氨酸缀合物（M4）。该代谢研究将有助于理解BBM诱导细胞毒性的生化机制。
