黄芩提取物中有效成分黄芩苷和汉黄芩苷在糖尿病大鼠中的药动学研究

Studies on the pharmacokinetic profiles of baicalin and wogonoside in diabetic rats after oral administration of extract of Scutellariae Radix

目的:比较黄芩提取物中主要成分黄芩苷和汉黄芩苷在糖尿病大鼠和正常大鼠体内的药动学。方法:腹腔注射链脲佐菌素建立糖尿病大鼠模型,灌胃黄芩提取物后取血分离血浆,采用HPLC-UV法检测血浆中黄芩苷和汉黄芩苷浓度,以矩量法计算药动学参数,AUC(0-τ)的计算采用梯形法。采用黄芩提取物与大鼠粪便温孵,从肠道代谢研究黄芩苷和汉黄芩苷动力学改变的初步机制。结果:与正常大鼠比较,糖尿病大鼠给予黄芩苷和汉黄芩苷后体内Cm ax1明显增加[黄芩苷:(6.07±0.95)vs.(17.01±3.60)μg.mL-1,P<0.01;汉黄芩苷:(3.50±0.72)vs.(9.34±2.04)μg.mL-1,P<0.01],Cm ax2明显增加[黄芩苷:(1.61±0.18)vs.(7.39±3.04)μg.mL-1,P<0.01;汉黄芩苷:(1.95±0.52)vs.(6.72±2.60)μg.mL-1,P<0.01],AUC(0-τ)也明显增加[黄芩苷:(38.72±7.25)vs.(86.70±20.91)μg.mL-1.h,P<0.01;汉黄芩苷:(39.20±12.10)vs.(69.40±24.20)μg.mL-1.h,P<0.01],粪便悬浮液中黄芩苷降解也加快(Ke:0.087 vs.0.173 m in-1)。结论:黄芩苷和汉黄芩苷在糖尿病大鼠与正常大鼠之间存在明显的药动学差异,在糖尿病大鼠肠道内代谢加快。

Objective：To investigate the pharmacokinetic profiles of baicalin and wogonoside in diabetic rats, which are two major constituents of the extract of Scutellariae radix （ ES）. Methods：The diabetic rats were induced by intraperitoneal administration streptozotocin. After the establishment of the method and the preparation of diabetic rats, the pharmacokinetic profiles of baicalin and wogonoside were investigated. Diabetic and control rats were orally administered with ES extract, and then the blood samples were collected at given time points. Plasma samples were obtained by centrifuging at 5 000 r· min^-1. Contents of baicalin and wogonoside in diabetic and control rat plasma were assayed by HPLC-UV method. The pharmacokinetic parameters were analyzed by non -compartmental method. Moreover, the presystemic metabolism of baicalin was investigated and compared to explore the pharmacokinetic difference by fermentation of ES in feces suspensions of control and diabetic rats, respectively. Results：The results indicated that C max1 , Cmax2, AUC（0-τ） of baicalin and wogonoside in diabetic rats were significantly enhanced when compared with control rats. The parameters of control rats and diabetic rats were as follows： Cmax1[baicalin：（6.07 ±0.95） vs. （17.01 ±3.60） μg·mL^-1,P 〈0.01;wogonoside：（3.50 ±0.72） vs. （9.34±2.04） μg·mL^-1,P〈0.01J,Cmax2[baicalin：（1.61 ±0.18） vs. （7.39±3.04）μg·mL^-1, P〈0.01;wogonoside：（1.95 ±0.52） vs. （6.72 ±2.60） μg·mL^-1,P 〈0.01],AUC（0-τ）[baicalin： （38.72±7.25） vs. （86.70±20.91）μg·mL^-1·h,P〈0.01;wogonoside：（39.20±12.10） vs. （69. 40 ±24.20） μg·mL^-1·h,P〈0.01],Ko（baicalin：0.087 vs. 0.173 min^-1）. Conclusion：The pharmacokinetic difference of baicalin and wogonoside in diabetic and control rats was significant. The baicalin and wogonoside in the intestine of diabetic rats have more rapid metabolism.