Su Su, Wang Yanan, Bai Lu, Xia Binbin, Li Xiaorong, Tang Yu, Xu Pingxiang, Xue Ming
Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
J Pharm Biomed Anal. 2015 Feb;104:38-46. doi: 10.1016/j.jpba.2014.11.010. Epub 2014 Nov 15.
Isobavachalcone (IBC) is a prenylated chalcone and belongs to the class of flavonoids, which is an active component isolated from Psoralea corylifolia L. IBC showed a range of significant pharmacological activities, including antibacterial, anticancer, anti-reverse transcriptase and antioxidant actions. In this research, the mass spectral fragmentation pattern of IBC was investigated to predict the in vivo metabolites, and five phase I metabolites and ten phase II metabolites of IBC in rat bile were elucidated and identified after oral administration using novel LC-ESI-MS(n) and LC-NMR method. The molecular structures of these metabolites were proposed on the basis of the characteristics of their precursor ions, product ions, MS/MS fragment behaviors and chromatographic retention time. The phase I metabolites were mainly biotransformed via the hydroxylation, reduction, cyclization and oxidative cleavage reactions. The phase II metabolites were mainly identified as the glucuronide conjugates and sulfated conjugates. All these findings were reported for the first time and would contribute to a further understanding of the in vivo intermediate processes and metabolic mechanism of isobavachalcone and its analogs.
异补骨脂查耳酮（IBC）是一种异戊烯基查耳酮，属于黄酮类化合物，是从补骨脂中分离出的一种活性成分。IBC具有一系列显著的药理活性，包括抗菌、抗癌、抗逆转录酶和抗氧化作用。在本研究中，对IBC的质谱裂解模式进行了研究以预测其体内代谢产物，采用新型液相色谱-电喷雾串联质谱（LC-ESI-MS(n)）和液相色谱-核磁共振（LC-NMR）方法，在大鼠口服给药后阐明并鉴定了IBC在大鼠胆汁中的5种I相代谢产物和10种II相代谢产物。根据这些代谢产物的前体离子、产物离子、串联质谱碎片行为和色谱保留时间的特征，推测了它们的分子结构。I相代谢产物主要通过羟基化、还原、环化和氧化裂解反应进行生物转化。II相代谢产物主要鉴定为葡萄糖醛酸苷缀合物和硫酸化缀合物。所有这些发现均为首次报道，将有助于进一步了解异补骨脂查耳酮及其类似物的体内中间过程和代谢机制。
