苦荞提取物中槲皮素在糖尿病大鼠体内的药动学研究

Studies on the pharmacokinetic profiles of quercetin in diabetic rats after oral administration of extract of Fagopyrum tataricum(L.) Gaertn

目的比较苦荞提取物中槲皮素在正常大鼠和糖尿病大鼠体内的药动学。方法将15只雄性SD大鼠分为模型组(n=10)和对照组(n=5)。模型组10只大鼠通过高脂高糖饲料喂养联合腹腔注射链脲佐菌素(streptozotocin,STZ)建立糖尿病大鼠模型,灌胃苦荞提取物后取血分离血浆,采用高效液相色谱法(high performance liquid chromatography,HPLC)测定槲皮素血药浓度,经3P97软件处理数据。结果苦荞提取物中槲皮素在正常大鼠和糖尿病大鼠体内的药动学参数分别为峰浓度(Cmax1=1.022±0.280 mg/L)、药-时曲线下面积(AUC0-12=5.982±2.361 mg·h/L)、消除半衰期(t1/2β=32.874±11.251 h)和峰浓度1(Cmax1=1.477±0.356 mg/L)、峰浓度2(Cmax2=0.602±0.090 mg/L)、药-时曲线下面积(AUC0-12=10.248±4.103 mg·h/L)、消除半衰期(t1/2β=53.381±12.562 h),结果表明大鼠在糖尿病病理状态下槲皮素的Cmax1、Cmax2、AUC0-12明显增加,消除半衰期显著增长。结论槲皮素在糖尿病大鼠和正常大鼠体内的药动学有显著差异,可能与糖尿病大鼠的肝、肾功能受损有关,提示临床用药时应适当减小糖尿病患者槲皮素的用量。

Objective To investigate the pharmacokinetics profiles of quercetin in normal rats and diabetic rats, which is the major constituent of the extract of Fagopyrum tataricum（L.） Gaertn. Methods 15 male SD rats were divided into model group（n=10） and control group（n=5）. The rats of model group were fed by high fat diet and intraperitoneal administration streptozotocin（STZ）. Diabetic and control rats were orally administered with the extract of Fagopyrum tataricum（L.） Gaertn., and then the blood samples were collected at given time points. Content of quercetin in diabetic and control rat plasma was assayed by high performance liquid chromatography（HPLC） method. The pharmacokinetic parameters were analyzed by 3P97. Results The pharmacokinetic paramaters of of quercetin of the extract of Fagopyrum tataricum（L.） Gaertn. in normal rats and diabetic rats were respectively as following： peak concentration（Cmax1） was 1.022±0.280 mg/L, area under the concentration-versus-time curve（AUC0-12） was 5.982±2.361 mg·h/L, elimination half life（t1/2β） was 32.874±11.251 h in normal rats, and peak concentration（Cmax1） was 1.477±0.356 mg/L, peak concentration（Cmax2） was 0.602±0.090 mg/L, area under the concentration-versus-time curve（AUC0-12） was 10.248±4.103 mg·h/L, elimination half life（t1/2β） was 53.381±12.562 h in diabetic rats. The results indicated that Cmax1, Cmax2 and AUC0-12 of quercetin in diabetic rats were enhanced and t1/2β of quercetin was remarkably extended when compared with control rats. Conclusions Quercetin has significantly different pharmacokinetics in diabetic rats and normal ones owing to the damage of the liver and kidney of diabetic rats, which suggests the dose of quercetin should be reduced when administration in diabetic patients.