黄芪甲苷的生物样品稳定性考察及在大鼠体外肠菌中代谢转化研究  

Stability study in biological samples and metabolites analysis of astragaloside Ⅳ in rat intestinal bacteria in vitro

作　　者：孙桂霞[1] 赵园园[1] 苗培培 杨晓燕[1] 苗青[1] 李静[2] 薛宝娟[1] 苏谨[1] 张玉杰[1] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]北京积水潭医院中药房,北京100035

出　　处：《中国中药杂志》2014年第21期4258-4264,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81073140;81274177)

摘　　要：为明确黄芪甲苷(AST)在生物样品中的稳定性和在大鼠体外肠菌代谢转化产物及代谢途径。本实验采用体外的方法对AST在人工胃液、人工肠液及大鼠肝匀浆中的稳定性以及大鼠离体肠道菌群中的代谢产物进行探讨。采用HPLC法测定AST在生物样本中的含量,计算AST在生物样本中的剩余百分率。采用TLC,HPLC和LC-MS/MS相结合的分析手段,鉴定代谢产物。结果发现,AST在人工胃液、人工肠液及肝脏中均较稳定,不易代谢;AST肠道菌群的代谢是通过脱糖基逐级进行的。首先,失去3位木糖基转化成次生代谢产物环黄芪醇-6-O-β-D-吡喃葡萄糖苷(CMG)。然后,失去6位葡萄糖基得到极性更小的皂苷元环黄芪醇(CAG)。研究结果表明AST在体内主要在肠道代谢,发生糖基水解作用。即肠道菌群的水解作用是AST代谢的主要原因。To figure out the stability and intestinal bacteria metabolites of rats in vitro of astragaloside 1V （ AST）, this research was done to explore the stability of AST in the artificial gastric juice artificial intestinal juice and rat liver homogenate and the metabolism in rat intestinal in vitro. HPLC was used to calculate the remaining rate of AST in biological samples by measuring the content of AST, while metabolites were determined by combining the methods of TLC, HPLC and LC-MS/MS. It turned out that AST was difficult to metabolize in the artificial gastric juice, artificial intestinal juice and rat liver. Also, the metabolic pathway of AST was stepped by deglycosylation. Firstly, AST was converted to its secondary etabolites （6-O-β-D-glucopyranosyl- cycloastragenol, CMG） by removal of xylose moiety at C-3, then transformed into cycloastragenol （CAG） after hydrolytic removal of the glucose moiety at C-6. All the results suggested that the metabolism of AST in vivo occurs mainly in the intestinal by hydrolysis of glycosyl. In conclusion, hydrolysis of intestinal flora is the main reason that AST metabolizes.

关 键 词：黄芪甲苷 稳定性 体外 肠菌代谢 代谢产物 代谢途径 

分 类 号：R282.7[医药卫生—中药学]