Wang Kun, Chai Liwei, Feng Xinchi, Liu Zhongbo, Liu Hongxia, Ding Liqin, Qiu Feng
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China.
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China.
J Pharm Biomed Anal. 2017 May 30;139:73-86. doi: 10.1016/j.jpba.2017.02.038. Epub 2017 Feb 27.
Berberine (BBR), the principle component for many medicinal plants such as Coptis chinensis Franch., Phellodendron chinense Schneid., and Mahonia bealei (Fort.) Carr., possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic and antidiabetic activities. In this study, a rapid and reliable method using a five-step strategy based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), and metabolynx™ software with mass defect filter (MDF) technique was developed to investigate the metabolism of BBR. Plasma, bile, urine and feces samples were collected from rats after oral administration of BBR with a dose of 100mg/kg/day for three consecutive days and analyzed to characterize the metabolic profile of BBR. By comparing the molecular weights and MS fragmentations of the metabolites with those of the parent drug and reference standards, a total of 97 metabolites were identified, including 68 metabolites in urine, 45 metabolites in plasma, 44 metabolites in bile and 41 metabolites in feces. Demethylation, demethylenation, reduction, hydroxylation, and subsequent glucuronidation, sulfation and methylation were the major metabolic pathways of BBR in vivo.
黄连素（BBR）是黄连、黄柏和三颗针等多种药用植物的主要成分，具有多种药理活性，包括抗菌、抗炎、抗肿瘤、降血脂和抗糖尿病活性。在本研究中，开发了一种基于超高效液相色谱-四极杆飞行时间质谱联用（UPLC/Q-TOF-MS）的五步策略和带有质量缺陷过滤器（MDF）技术的metabolynx™软件的快速可靠方法，以研究BBR的代谢情况。连续三天以100mg/kg/天的剂量给大鼠口服BBR后，收集血浆、胆汁、尿液和粪便样本并进行分析，以表征BBR的代谢谱。通过比较代谢产物与母体药物和参考标准品的分子量和质谱碎片，共鉴定出97种代谢产物，包括尿液中的68种代谢产物、血浆中的45种代谢产物、胆汁中的44种代谢产物和粪便中的41种代谢产物。去甲基化、去亚甲基化、还原、羟基化以及随后的葡萄糖醛酸化、硫酸化和甲基化是BBR在体内的主要代谢途径。
