Zhang Jing, Wen Quan, Xu Xu, Chen Lin, Feng Yu-Lin, Yang Shi-Lin, Luo Yun, Tan Ting
The National Pharmaceutical Engineering Center (NPEC) for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
Zhongguo Zhong Yao Za Zhi. 2018 Nov;43(21):4330-4338. doi: 10.19540/j.cnki.cjcmm.20180815.005.
Scopolin (SC-1), scopoletin (SC-2) and isofraxidin (IS-1) are the main active constituents in Chimonanthi Radix. However, the in vivo metabolism of SC-1, SC-2 and IS-1 have not been comprehensively clarified. In this study, the in vivo metabolic profiles of these three coumarins in the rat plasma, urine and feces were analyzed. Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS) method was applied to characterize the prototypes and metabolites of SC-1, SC-2 and IS-1 in rat feces, urine, and plasma after intravenous administration. A total of 11 metabolites of the three parent compounds were tentatively identified. The main metabolic pathways were analyzed by identification of metabolites, and it was found that these three coumarins underwent multiple in vivo metabolic reactions including glucuronidation, sulfonation, isomerism and reduction. In this study, the analysis of metabolites of three coumarins basically demonstrated their in vivo metabolic process, providing basis for the further pharmacokinetics and pharmacological evaluations of SC-1, SC-2 and IS-1.
东莨菪苷(SC - 1)、东莨菪素(SC - 2)和异秦皮啶(IS - 1)是腊梅根中的主要活性成分。然而,SC - 1、SC - 2和IS - 1的体内代谢尚未得到全面阐明。本研究分析了这三种香豆素在大鼠血浆、尿液和粪便中的体内代谢谱。采用超高效液相色谱 - 四极杆飞行时间质谱(UHPLC - QTOF - MS/MS)方法对静脉给药后大鼠粪便、尿液和血浆中SC - 1、SC - 2和IS - 1的原型和代谢产物进行表征。初步鉴定出三种母体化合物的11种代谢产物。通过代谢产物的鉴定分析主要代谢途径,发现这三种香豆素在体内经历了多种代谢反应,包括葡萄糖醛酸化、磺化、异构化和还原反应。本研究对三种香豆素代谢产物的分析基本阐明了它们的体内代谢过程,为SC - 1、SC - 2和IS - 1进一步的药代动力学和药理学评价提供了依据。