芙朴感冒颗粒中橙皮苷小肠吸收特征研究  

Characteristics of the intestinal absorption of Hesperidin from Fupu Ganmao granules

作　　者：余蓓萌 周萍[2] 潘海滔 徐人杰 YU Bei-meng;ZHOU Ping;PAN Hai-tao;XU Ren-jie(Neonatal Intensive Care Unit,Shaoxing Maternity and Child Health Care Hospital,Shaoxing 312000,China;Department of Clinical Pharmacy,Shaoxing Maternity and Child Health Care Hospital,Shaoxing 312000,China;Medical Research and Achievement Transformation Center,Shaoxing Maternity and Child Health Care Hospital,Shaoxing 312000,China)

机构地区：[1]绍兴市妇幼保健院新生儿监护中心,浙江绍兴312000 [2]绍兴市妇幼保健院临床药学室,浙江绍兴312000 [3]绍兴市妇幼保健院医学研究与成果转化中心,浙江绍兴312000

出　　处：《实用药物与临床》2022年第1期77-82,共6页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金课题(81701522)。

摘　　要：目的研究芙朴感冒颗粒中的橙皮苷跨膜吸收特征及其影响因素。方法使用Caco-2细胞模型考察橙皮苷的小肠吸收,研究不同药物浓度、pH值、温度和抑制剂对橙皮苷在transwell细胞培养板中从顶膜(AP)到基底(BL)的双向渗透吸收的影响。采用药动学实验研究芙朴感冒颗粒在体内对橙皮苷吸收的影响。结果橙皮苷以3种测试浓度给药时(1、10、100μmol/L),从AP到BL方向的表观渗透系数(P _(app))值范围为:1.20×10^(-6)~1.30×10^(-6) cm/s。相反,从BL到AP,P _(app)值范围为:2.23×10^(-6)~2.81×10^(-6) cm/s,表明橙皮苷转运具有pH和温度依赖性。橙皮苷的细胞通透性受多种抑制剂影响,包含P-糖蛋白(P-gp)抑制剂维拉帕米及乳腺癌耐药蛋白(BCRP)抑制剂芹菜素。当芙朴感冒颗粒溶液加入后,橙皮苷的吸收显著增加。在药动学实验中,芙朴感冒颗粒组的橙皮苷相对于单体组有更大的吸收入血暴露量。结论橙皮苷属于中等吸收化合物,其小肠吸收特征包含主动外排转运,同时芙朴感冒颗粒中某些成分会显著促进橙皮苷的吸收。Objective To study the absorption of hesperidin and the the influencing factors of hesperidin′s absorption.Methods Caco-2 cell model was used to examine the intestinal absorption of Hesperidin.The effects of concentration,pH,temperature and inhibitors on the bidirectional permeability of hesperidin from the apical(AP)to the basolateral(BL)side and in the reverse direction were studied.A pharmacokinetic study was developed to investigate the effect of Fupu Ganmao granules on hesperidin′s absorption in vivo.Results When administered at three tested concentrations(1,10,100μmol/L),the apparent permeability coefficient(P_(app))values in the AP-to-BL direction ranged from 1.20×10^(-6)to 1.30×10^(-6)cm/s.In the reverse direction,BL-to-AP,the value ranged from 2.23×10^(-6)to 2.81×10^(-6)cm/s.The data indicated that hesperidin transport was pH-and temperature-dependent.The permeability of hesperidin was affected by treatment with various inhibitors,such as P-gp inhibitors verapamil and the breast cancer resistance protein inhibitor apigenin.After the addition of Fupu Ganmao granules,the P app values in the AP-to-BL direction increased significantly.Hesperidin showed a higher systemic exposure in Fupu Ganmao granules than in hesperidin group in pharmaco-dynamic experiment.Conclusion Hesperidin is considered to have a moderate absorption and the intestinal absorption feature is mainly the efflux of hesperidin.At the same time,some ingredients in Fupu Ganmao granules promote hesperidin′s absorption significantly.

关 键 词：橙皮苷 CACO-2 口服 吸收机制 

分 类 号：R285[医药卫生—中药学]