多药耐药相关蛋白2对汉黄芩素及其主要Ⅱ相代谢产物药动学特征的影响  

Effect of multidrug resistance protein 2 on pharmacokinetics of wogonin and its major phase Ⅱ metabolites

作　　者：郑蓉 张淇淞 胡雪黎 徐睿 彭国爽 昌冰琳 胡泽华 胥鑫林 杨宝 ZHENG Rong;ZHANG Qi-song;HU Xue-li;XU Rui;PENG Guo-shuang;CHANG Bing-lin;HU Ze-hua;XU Xin-lin;YANG Bao(Medical School,Hubei Minzu University,Enshi 445000,China;Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases,Hubei Minzu University,Enshi 445000,China;Medical College,Guangxi University,Nanning 530004,China;School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]湖北民族大学医学部,湖北恩施445000 [2]湖北民族大学,风湿性疾病发生与干预湖北省重点实验室,湖北恩施445000 [3]广西大学医学院,广西南宁530004 [4]广州中医药大学中药学院,广东广州510006

出　　处：《中草药》2022年第21期6779-6784,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81560703):湖北民族大学大学生创新创业训练计划项目(S202110517027);广西大学高层次人才基金项目(A3370051006):风湿性疾病发生与干预湖北省重点实验室(湖北民族大学)项目(PT022202)。

摘　　要：目的 研究多药耐药相关蛋白2(multidrug resistance protein 2,MRP2)对汉黄芩素及其主要Ⅱ相代谢产物药动学特征的影响。方法 FVB野生型和MRP2-/-小鼠ig汉黄芩素β-环糊精包合物后,于不同时间点眼眶取血。采用超高效液相色谱-质谱联用技术检测汉黄芩素、汉黄芩苷、汉黄芩素-7-O-硫酸酯的血药浓度,采用DAS 2.0软件以非房室模型计算药动学参数。结果 3个成分的线性关系良好,准确度、精密度、稳定性、回收率等符合要求。汉黄芩素主要以Ⅱ相代谢产物汉黄芩苷和汉黄芩素-7-O-硫酸酯存在,均在30 min内达到最大血药浓度。汉黄芩苷的达峰浓度(Cmax)和药时曲线下面积(AUC0~t)最高,汉黄芩素-7-O-硫酸酯次之,汉黄芩素最低。与FVB野生型组比较,MRP22-/-组汉黄芩苷和汉黄芩素-7-O-硫酸酯的Cmax和AUC0~t显著增加(P<0.05、0.01)。结论 MRP2介导了汉黄芩苷和汉黄芩素-7-O-硫酸酯的外排过程,显著影响汉黄芩素的体内处置过程。Objective To study the effect of multidrug resistance protein 2(MRP2)on pharmacokinetic behaviors of wogonin and its major phaseⅡmetabolites.Methods FVB wild-type and MRP2−/−mice were taken blood from eye sockets at different time points after ig wogonin withβ-cyclodextrin.The plasma concentrations of wogonin,wogonoside and wogonin-7-O-sulfate were determined by ultra-performance liquid chromatography coupled to mass spectrometry(UPLC-MS)method.The pharmacokinetic parameters were calculated by non-compartmental models with DAS 2.0 software.Results The linearity of three components was good,and accuracy,precision,stability and recovery rate met the requirements.Wogonin was mostly biotransformed to wogonoside and wogonin-7-O-sulfate and these analytes reached peak concentration(C_(max))within 30 min.The plasma Cmaxandarea under the curve(AUC0~t)of wogonoside were the highest,followed by wogonin-7-O-sulfate,and wogonin was the lowest.Compared with FVB wild-type group,Cmax and AUC0~t of wogonoside and wogonin-7-O-sulfate in MRP2−/−group were significantly increased(P<0.05,0.01).Conclusion MRP2 mediated the efflux of wogonoside and wogonin-7-O-sulfate,significantly affected the disposal process of wogonin in vivo.

关 键 词：汉黄芩素 汉黄芩苷 汉黄芩素-7-O-硫酸酯 药动学 多药耐药相关蛋白2 Ⅱ相代谢产物 

分 类 号：R285.61[医药卫生—中药学]