Lin Pei, Qin Zifei, Yao Zhihong, Wang Li, Zhang Weiyang, Yu Yang, Dai Yi, Zhou Hua, Yao Xinsheng
College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 May 15;1085:72-88. doi: 10.1016/j.jchromb.2018.04.001. Epub 2018 Apr 4.
Gualou Xiebai Baijiu decoction (GLXB), a well-known classic traditional Chinese medicine prescription, has been widely used to treat coronary heart diseases for thousands of years in Eastern Asian countries due to its remarkable clinical effect. However, due to lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. In this work, a reliable "representative structure based homologous xenobiotics identification" (RSBHXI) strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) were applied to investigate the chemical components in GLXB extracts. As a result, 133 chemical components were characterized based on summarized fragmentation patterns, of which 41 components were confirmed unambiguously with authentic standards. Furthermore, a total of 138 GLXB-related xenobiotics were identified or tentatively characterized after oral administration of GLXB extracts. Moreover, to better understand the metabolic pathways of characteristic components in GLXB, metabolites profiles of five steroidal saponins and two flavonoids were performed, respectively. Since the metabolic pathways of five representative saponins had been finished in our previous study, we focused on the in vivo metabolism of two flavonoids. A total of 36 and 20 metabolites were detected in rat biological samples after oral administration of luteolin-7-O-β-D-glucopyranoside and rutin, respectively. The results indicated that dehydration, hydrolysis, hydroxylation, methylation, glucuronidation and sulfation were the main metabolic reactions, following the metabolic soft spots of GLXB-related flavonoids. Taken altogether, this study would be helpful for the further pharmacokinetics, pharmacological evaluation and quality control of GLXB.
瓜蒌薤白白酒汤（GLXB）是一种著名的经典中药方剂，因其显著的临床疗效，在东亚国家已被广泛用于治疗冠心病达数千年之久。然而，由于缺乏体内代谢研究，其治疗作用的化学成分仍不清楚。在本研究中，基于超高效液相色谱-四极杆飞行时间串联质谱（UPLC/Q-TOF-MS）的可靠的“基于代表性结构的同源性外源性物质鉴定”（RSBHXI）策略被应用于研究GLXB提取物中的化学成分。结果，基于总结的碎片模式鉴定出133种化学成分，其中41种成分通过对照品得到明确确认。此外，口服GLXB提取物后，共鉴定或初步表征了138种与GLXB相关的外源性物质。此外，为了更好地了解GLXB中特征成分的代谢途径，分别对5种甾体皂苷和2种黄酮类化合物进行了代谢产物谱研究。由于我们之前的研究已经完成了5种代表性皂苷的代谢途径，因此我们重点研究了2种黄酮类化合物的体内代谢。大鼠口服木犀草素-7-O-β-D-吡喃葡萄糖苷和芦丁后，在大鼠生物样品中分别检测到36种和20种代谢产物。结果表明，脱水、水解、羟基化、甲基化、葡萄糖醛酸化和硫酸化是主要的代谢反应，这与GLXB相关黄酮类化合物的代谢软点一致。综上所述，本研究将有助于进一步开展GLXB的药代动力学、药理评价及质量控制研究。
