桑叶黄酮类和生物碱类成分在正常和糖尿病大鼠体内的药代动力学研究  

Pharmacokinetics of Mori Folium flavones and alkaloids in normal and diabetic rats

作　　者：张立雯 季涛[1] 宿树兰[1] 尚尔鑫[1] 郭盛[1] 郭建明[1] 钱大玮[1] 段金廒[1] 

机构地区：[1]南京中医药大学江苏省中药资源产业化过程协同创新中心/中药资源产业化与方剂创新药物国家地方联合工程研究中心国家中医药管理局中药资源循环利用重点研究室,江苏南京210023

出　　处：《中国中药杂志》2017年第21期4218-4225,共8页China Journal of Chinese Materia Medica

基　　金：江苏高校中药资源产业化过程协同创新中心建设专项;国家科技支撑计划项目(2012BAI29B02);江苏省"333高层次人才工程"项目(2013;2015);江苏高校中药学优势学科Ⅱ期建设工程(2014-ysxk)

摘　　要：采用UPLC-TQ-MS同时测定糖尿病模型大鼠和空白大鼠血浆中芦丁、异槲皮苷、紫云英苷、山柰酚、槲皮素、绿原酸、隐绿原酸、新绿原酸、DNJ、fagomine 10种有效成分,并计算其在大鼠体内药动学参数,以阐明桑叶黄酮类及生物碱类在正常和糖尿病模型大鼠体内的药代动力学特征。以高糖高脂饲料结合尾静脉注射四氧嘧啶的方法复制糖尿病模型,大鼠灌胃给予桑叶黄酮类及生物碱类成分的提取物后不同时间点取血浆,血浆样品经乙腈沉淀蛋白,以UPLC-TQ-MS测定血浆中桑叶10种成分的血药浓度,采用DAS 2.0软件计算药动学参数。结果显示,槲皮素和山柰酚灌胃0.333 h达到峰值,说明大鼠口服桑叶黄酮类成分后吸收和分布较为迅速;服药后4 h,两者第2次达到峰浓度,说明其在肠道内的停留时间较长;DNJ和fagomine在胃肠道能较快地吸收入血,血药浓度在0.667 h达到峰值,提示两者进入大鼠体循环后可快速分布。在模型组大鼠体内新绿原酸、隐绿原酸、槲皮素、山柰酚、芦丁的Cmax和AUC0–t降低,新绿原酸、隐绿原酸t1/2缩短,而槲皮素、山柰酚、芦丁的t1/2延长;绿原酸、紫云英苷、异槲皮苷、fagomine在模型动物体内Cmax升高,紫云英苷、fagomine的t1/2延长,提示在正常生理状态与模型病理状态下机体对药物有效成分的吸收存在一定的差异。To study the pharmacokinetic effect of Mori Folium flavones and alkaloids in normal and diabetic rats. An UPLC-TQ-MS method was developed for the simuhaneous deternfination of rutin, isoquereitrin, astragalin, kaempferol, quercetin, chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, DNJ and fagomine in plasma of rats. The diabetic rat model was induced through intrave- nous injection with alloxan and high-fat diet. Samples of plasma of rats were obtained at different time points, after the rats were admin- istrated with Mori Folium flavones and alkaloids. After the deproteinization with acetonitrile, the concentrations of Mori Foliam constitu- ents in rats at different time points were detected by UPLC-TQ-MS method, and pharmacokinetic parameters were calculated by DAS 2. 0 software. The results showed that quercetin and kaempferol reached peak at 0. 333 h, indicating that Mori Folium flavonoid constit- uents were absorbed and distributed quickly. At about 4 h after administration, both of them reached the peak concentrations for the second time, suggesting that they stayed in intestine for a long time. DNJ and fagomine in gastrointestinal tract can be quickly absorbed into blood, and the concentration in plasma reached peak after 0. 667 b, suggesting that both of them could be rapidly distributed in the systemic circulation of rats. Cryptochlorogenic acid, neochlorogenie acid, quercetin, kaempferol and rutin were found to have a higher C,,~ and AUC0_, in normal rats than those in diabetic rats. The tl/2values of cryptochlorogenic acid and neocblorogenic acid were shorter in diabetic rats, while quercetin, kaempferol and rutin had a longer t^2 value in diabetic rats. Chlorogenic acid, astragalin, isoquer- citrin, fagomine bad a higher Cmax in diabetic rats, and the t1/2 values of astragalin and fagomine were longer, which suggested differ- ences in absorption of active ingredients under normal and diabetic conditions.

关 键 词：桑叶 黄酮类 生物碱类 糖尿病 药动学 

分 类 号：R285.5[医药卫生—中药学]