中药多糖对葛根素口服生物利用度及其跨膜转运机制的影响  

Effect of Chinese medicine polysaccharide on pharmacokinetic behaviors and transmembrane mechanisms of puerarin

作　　者：何佳莹 袁芳英 刘湾[1] 程勐 刘美 金一 奉建芳 涂亮星 HE Jia-ying;YUAN Fang-ying;LIU Wan;CHENG Meng;LIU Mei;JIN Yi;FENG Jian-fang;TU Liang-xing(National Pharmaceutical Engineering Center for Solid Preparation Chinese Herbal Medicine,Jiangxi University of Chinese Medicine,Nanchang 330000,China;The Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330006,China;School of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,China;Sichuan Institute of Food Inspection,Chengdu 611731,China)

机构地区：[1]江西中医药大学中药固体制造技术国家工程研究中心,江西南昌330000 [2]江西中医药大学附属医院,江西南昌330006 [3]广西中医药大学药学院,广西南宁530200 [4]四川省食品检验研究院,四川成都611731

出　　处：《中草药》2022年第15期4738-4745,共8页Chinese Traditional and Herbal Drugs

基　　金：江西省主要学科学术和技术带头人培养计划项目(20212BCJL23060);江西中医药大学“1050”青年人才工程项目(5142001012);江西中医药大学博士启动项目(2018BSZR018)。

摘　　要：目的 通过研究6种中药多糖(人参多糖、白芨多糖、茶多糖、大豆多糖、枸杞多糖、葛根多糖)对葛根素在大鼠体内的药动学变化,探讨中药多糖对葛根素口服吸收的影响,并采用犬肾MDCK细胞单层模型研究了中药多糖的促口服吸收机制。方法 大鼠ig葛根素及不同中药多糖-葛根素混悬液后,于不同时间点采集血样,经适当处理后,采用高效液相色谱(HPLC)测定血浆中葛根素的质量浓度,并以此计算和比较药动学参数。采用MDCK细胞单层模型考察中药多糖借助葡萄糖转运提高葛根素跨膜吸收的能力。结果 与中药多糖联合给药后,葛根素的主要药动学参数有不同程度的变化,主要呈现出促进葛根素口服吸收的趋势,其中以人参多糖的促吸收效果最为卓越,人参多糖可将葛根素的达峰浓度(Cmax)及曲线下面积(AUC_(0~∞))分别提高1.77及3.14倍。CCK-8实验表明药物质量浓度为5~1000μg/mL、人参多糖质量浓度为20~10 000μg/mL时,药物及多糖无明显细胞毒性。在50~1000μg/mL质量浓度内,葛根素的表观渗透系数(apparent permeability coefficient,P_(app))无明显变化;人参多糖可将葛根素的P_(app)显著升高(P<0.05、0.01、0.001);加入葡萄糖转运抑制剂(根皮素、根皮苷)后,葛根素组的P_(app)无明显变化,而人参多糖组的P_(app)显著下降(P<0.001)。结论 中药多糖会通过葡萄糖转运途径提高葛根素的口服吸收,提示利用中药多糖作为递药系统修饰剂,或许可成为一种有潜力的提高难吸收药物口服吸收的技术手段。Objective To explore the effect of traditional Chinese medicine polysaccharide on oral absorption of puerarin by studying the effect of six kinds of traditional Chinese medicine polysaccharide(ginseng polysaccharide, Bletilla striata polysaccharide, tea polysaccharide, soybean polysaccharide, Lycium barbarum polysaccharide, Pueraria lobata polysaccharide) on pharmacokinetic changes of puerarin in rats. And to study the mechanism of promoting oral absorption of traditional Chinese medicine polysaccharides by using canine kidney MDCK cell monolayer model. Methods After ig puerarin and different traditional Chinese medicine polysaccharide-puerarin suspensions, blood samples were collected at different time points. After appropriate treatment, concentration of puerarin in plasma was determined by high performance liquid chromatography(HPLC), pharmacokinetic parameters were calculated and compared. MDCK cells monolayer model was used to investigate the ability of traditional Chinese medicine polysaccharides to enhance the transmembrane absorption of puerarin through glucose transport. Results After co-administration with traditional Chinese medicine polysaccharides, main pharmacokinetic parameters of puerarin were changed to varying degrees,mainly showing a trend of promoting oral absorption of puerarin. Among them, ginseng polysaccharide had the most excellent absorption promoting effect. Peak concentration(Cmax) and area under the curve(AUC_(0~∞)) were increased by 1.77 and 3.14 times.CCK-8 experiment showed that when the concentration of drug was 5—1000 μg/mL and concentration of ginseng polysaccharide was 20—10 000 μg/mL, drug and polysaccharide had no obvious cytotoxicity. Within the concentration of 50—1000 μg/mL, apparent permeability coefficient(P_(app)) of puerarin had no significantly changed;Ginseng polysaccharide significantly increased P_(app) of puerarin(P < 0.05, 0.01, 0.001);After adding glucose transport inhibitors(phloretin, phlorizin), P_(app) in puerarin group had no significant changed,

关 键 词：人参多糖 白芨多糖 茶多糖 大豆多糖 枸杞多糖 葛根多糖 葛根素 药动学 MDCK细胞单层 转运机制 葡萄糖转运途径 

分 类 号：R285.5[医药卫生—中药学]