Jiang Shu, Xu Jun, Qian Da-Wei, Shang Er-Xin, Liu Pei, Su Shu-Lan, Leng Xue-Jiao, Guo Jian-Ming, Duan Jin-Ao, Du Leyue, Zhao Min
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Aug 15;965:27-32. doi: 10.1016/j.jchromb.2014.05.028. Epub 2014 May 23.
Scutellaria-coptis herb couple is widely used traditional Chinese medicine (TCM) in treating type 2 diabetes; however, the in vivo integrated metabolism of its main bioactive components in type 2 diabetic rats remains unknown. In this paper, ultra-performance liquid chromatography (UPLC) coupled to quadrupole time-of-flight (Q-TOF) and the MetaboLynx™ software combined with mass defect filtering (MDF) together provided unique high throughput capabilities for drug metabolism study with excellent MS mass accuracy and enhanced MS(E) data acquisition. This rapid automated analysis method was successfully applied for screening and identification of the absorbed and metabolized constituents after oral administration of scutellaria-coptis extract to rats. The results showed that a total of 14 metabolites of two parent compounds were detected and tentatively identified in vivo based on the characteristics of their protonated ions. Main parent components of scutellaria-coptis extract such as baicalin and berberine were absorbed into the blood circulation of the rats. Differences of metabolite classes were not observed between normal and type 2 diabetic rat plasma and urine samples. However, the concentrations of baicalin and methylated berberine in type 2 diabetic rat plasma were much higher than those in normal sample. While, the concentrations of these two compounds in type 2 diabetic rat urine were remarkably lower than those in normal sample. This helped maintain a high blood drug concentration which might be beneficial for the treatment of type 2 diabetes. Additionally, the developed method was simple and reliable, revealing that it could be used to rapid screen and propose the structures of active components responsible for pharmacological effects of scutellaria-coptis and to better clarify its action mechanism. This work suggests that the integrative metabolism approach makes a useful template for drug metabolism research of TCMs.
黄芩-黄连药对是治疗2型糖尿病的常用中药；然而，其主要生物活性成分在2型糖尿病大鼠体内的整体代谢情况仍不清楚。本文中，超高效液相色谱（UPLC）与四极杆飞行时间（Q-TOF）联用以及MetaboLynx™软件结合质量亏损过滤（MDF）共同为药物代谢研究提供了独特的高通量能力，具有出色的质谱质量准确性和增强的质谱/质谱（MS(E)）数据采集功能。这种快速自动化分析方法成功应用于大鼠口服黄芩-黄连提取物后吸收和代谢成分的筛选与鉴定。结果表明，基于质子化离子的特征，在体内共检测并初步鉴定出两种母体化合物的14种代谢产物。黄芩-黄连提取物的主要母体成分如黄芩苷和小檗碱被吸收进入大鼠血液循环。正常大鼠和2型糖尿病大鼠血浆及尿液样本之间未观察到代谢产物类别的差异。然而，2型糖尿病大鼠血浆中黄芩苷和甲基化小檗碱的浓度远高于正常样本。同时，这两种化合物在2型糖尿病大鼠尿液中的浓度显著低于正常样本。这有助于维持较高的血药浓度，可能对2型糖尿病的治疗有益。此外，所建立的方法简单可靠，表明其可用于快速筛选并推测黄芩-黄连药理作用活性成分的结构，更好地阐明其作用机制。这项工作表明，整体代谢方法为中药的药物代谢研究提供了一个有用的模板。
