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目的野黄芩素在机体内被吸收后迅速发生Ⅱ相代谢结合反应。本实验研究野黄芩素主要的Ⅱ相代谢磺酸化代谢反应特征。方法采用FVB/NCrlVr(FVB)小鼠肠灌流模型及FVB/NCrlVr小鼠肝脏S9体外反应体系,HPLC-MS/MS及HPLC-UV测定汉黄芩素及其代谢产物,研究汉黄芩素主要的Ⅱ相代谢之一磺酸化代谢反应的特征。结果小鼠在体灌流实验中,野黄芩素的磺酸化代谢产物在小肠的外排速率与葡萄糖醛酸化代谢产物的外排速率无显著性差异(P=0.435),且结肠灌流液中仅检测到野黄芩素磺酸化代谢产物。野黄芩素在肠道吸收后原型药物与代谢产物均有部分经胆汁排泄。体外FVB/NCrlVr小鼠肝脏S9孵育实验中,20μmol.L-1的野黄芩素的磺酸化代谢反应速度显著高于10,40μmol.L-1时的反应速率(P<0.05)。结论本实验首次发现磺酸化代谢是野黄芩素在肠道内的主要代谢方式之一,野黄芩素经肠道吸收后存在肝肠循环。体外肝脏S9孵育的野黄芩素磺酸化反应可能存在底物抑制现象。
Purpose Bupleicin is rapidly absorbed in the body phase Ⅱ metabolic binding reaction. In this study, the main Phase Ⅱ metabolic sulfated metabolic reaction of baicalein was studied. Methods The intestinal perfused rat models of FVB / NCrlVr (FVB) mice and the liver S9 reaction system of FVB / NCrlVr mice were established. The contents of wogonin and its metabolites were determined by HPLC-MS / MS and HPLC-UV. Phase Metabolism One of the Metabolites of Sulfonation Metabolism. Results In vivo perfusion experiments, there was no significant difference (P = 0.435) between the efflux rate of sulfated metabolites of Scutellaria baicalensis and the efflux rate of glucuronidation metabolites in mice and only in colon perfusate To wild baicalein sulfonation metabolites. Wild baicalein in the intestinal absorption of the prototype drugs and metabolites are excreted by the bile. In the in vitro S9 incubation experiment in FVB / NCrlVr mice, the sulfated metabolic rate of 20 μmol·L-1 baicalein was significantly higher than that of 10 and 40 μmol·L-1 (P <0.05). CONCLUSIONS For the first time, sulfonated metabolism was found to be one of the major metabolic pathways of baicalein in the intestine. Baicalein was found to enter into the intestine and enterohepatic circulation after intestinal absorption. In vitro liver S9 incubation of baicalein sulfonation reaction may exist substrate inhibition phenomenon.