汉黄芩素在FVB小鼠体内的磺酸化代谢特征研究  

Sulfation metabolism features of wogonin in FVB mice

作　　者：谢利霞[1] 周娟[2] 柳茜[2] 冯潜[2] 夏笔军[2] 范艳芳[2] 

机构地区：[1]广东药学院附属南山人民医院药剂科,深圳518052 [2]南方医科大学药学院,广州510515

出　　处：《世界临床药物》2012年第7期406-411,共6页World Clinical Drug

基　　金：国家自然科学基金面上项目(基金编号:30873321)

摘　　要：目的探讨汉黄芩素Ⅱ相代谢中主要的磺酸化代谢反应特征。方法采用FVB小鼠肠灌流模型及FVB小鼠肝脏S9体外反应体系,通过采用高效液相色谱-质谱法(HPLC-MS/MS)和高效液相色谱-二极管阵列检测器(HPLC-DAD)测定汉黄芩素及其代谢产物,研究汉黄芩素主要的Ⅱ相代谢反应之一磺酸化代谢反应的特征。结果汉黄芩素在FVB小鼠小肠均发生葡萄糖醛酸化与磺酸化代谢反应,其中磺酸化代谢产物的排出速率为[(3.46±0.16)nmol/30 min/10 cm]。而汉黄芩素在结肠中只检测出磺酸化代谢产物,其排出速率为[(1.40±0.24)nmol/30 min/10 cm]。体外试验显示,汉黄芩素的磺酸化代谢符合双相酶代动力学特征,由两种磺酸化转移酶(Sult)亚型介导。结论汉黄芩素的磺酸化代谢反应是汉黄芩素肠道代谢的重要组成部分,其在肝脏的磺酸化代谢由两种Sult酶催化完成。Objective To investigate the sulfation metabolism features of wogonin in FVB mice. Methods FVB mouse intestinal perfusion models and incubation system with FVB mouse liver S9 fractions were adapted to conduct the study. HPLC-MS/MS and HPLC/DAD were used to identify and quantify wogonin and its metabolites in samples, as well as the ADAPT Ⅱ program to determine the kinetic parameters of sulfation. Results Both glucuronidation and sulfation of wogonin were detected in perfusate samples of small intestine, the excretion rate of sulfation metabolites was （3.46＋ 0.16） nmol/30 mird1 0 cm. But only sulfation metabolites could be detected in colon with an excretion rate of （1.40＋0.24） nmol/30min/10 era. The study in vitro showed that the sulfation metabolism ofwogonin was mediated by two isoforms of sulfotransferases （Sults）. Conclusion Sulfation is an important phase Ⅱmetabolism of wogonin, which is catalyzed by two isoforms of Sults.

关 键 词：汉黄芩素 磺酸化代谢 肠灌流 肝匀浆上清液(S9) 

分 类 号：R285.5[医药卫生—中药学]