基于UHPLC-Q-Orbitrap HRMS技术探究芪葛汤在高脂血症大鼠中的入血成分及其代谢产物

Exploring the ingredients absorbed into blood and their metabolites of Qige decoction in hyperlipidemia rats based on UHPLC-Q-Orbitrap HRMS

关键词:  UHPLC-Q-Orbitrap HRMS  芪葛汤  高脂血症  入血成分  代谢产物

Key words:  UHPLC-Q-Orbitrap HRMS  qige decoction  hyperlipidemia  ingredients absorbed into blood  metabolites.

摘要:

目的 探究和表征芪葛汤在高脂血症大鼠中的入血成分,为其药效物质基础研究提供参考。方法 以HFD喂养致高脂血症大鼠 SD 大鼠为实验对象,灌胃给予芪葛汤并收集血清样品,利用UHPLC-Q-Orbitrap HRMS技术分析鉴定吸收入血的原形成分及其代谢产物。结果 共鉴定出46个化学成分,其15个为原型成分,31个为代谢产物。15个原型成分中7个来自黄芪,5个来自葛根,3个来自广陈皮,31个代谢产物主要是来自含有毛蕊异黄酮、毛蕊异黄酮葡萄糖苷、染料木素、葛根素、大豆苷元、川陈皮素、橙皮素等结构单元的化合物代谢物。其主要代谢途径为羟基化、还原反应、氧化反应、水解反应、去甲基反应、糖醛酸化及其复合反应、葡萄糖醛酸化及其复合反应。结论 毛蕊异黄酮、毛蕊异黄酮葡萄糖苷、染料木素、葛根素、大豆苷元、川陈皮素、橙皮素在大鼠体内主要代谢途径为Ⅰ相和Ⅱ相代谢。该方法能快速分析芪葛汤的入血成分及其代谢产物,为进一步阐明治疗高脂血症葛根汤的药效物质基础及其作用机制提供了参考。

Abstract:

ABSTRACT: OBJECTIVE To profile and characterize the ingredients absorbed into blood and their metabolites of Qige Decoction in hyperlipidemia rats, and so as to provide a reference for investigation of the pharmacodynamicsubstances of Qige Decoction. METHODS SD rats with hyperlipidemia induced by HFD feeding were intragastrically administered with Qige decoction，and the rat plasma samples were collected and analyzed by UHPLC-Q-Orbitrap HRMS to identify the prototype ingredients absorbed into blood and their metabolites. RESULTS The results showed that 46 chemical components were identified, of which 15 were prototype components and 31 were metabolites. Among the 15 prototype components, 7 were from Astragali Radix, 5 were from Puerariae Lobatae Radix, 3 were from Citri reticulatae Chachiensis pericarpium, the 31 metabolites were mainly derived from complex metabolites, which contained structural units including Calycosin, Calycosin 7-O-Glucoside, Genistein, Puerarin, Daidzein, Nobiletin and Hesperetin. The main metabolic pathways are hydroxylation, reduction reaction, oxidation reaction, hydrolysis reaction, demethylation reaction, uronidation and its complex reaction, glucuronidation and its complex reaction. CONCLUSION The main metabolic pathways of Calycosin, Calycosin 7-O-Glucoside, Genistein, Puerarin, Daidzein, Nobiletin and Hesperetin in rats are phase Ⅰ and phase Ⅱ metabolism. This method can quickly analyze the ingredients absorbed into blood and their metabolites of Qige Decoction, laying a basis for elucidating the therapeutic material basis and mechanism of Qige Decoction.