调血脂类中药及中药单体对羧酸酯酶1体外活性抑制作用研究  

Inhibitory Effects of Extracts and Monomers from Lipid-lowering Chinese Medical Materials on Human Carboxylesterase 1 in Vitro

作　　者：王汇滨 许汉卿 马佳睿 张昕彤 贺智承 于青 邹立伟 刘东春[4] WANG Hui-bin;XU Han-qing;MA Jia-rui;ZHANG Xin-tong;HE Zhi-cheng;YU Qing;ZOU Li-wei;LIU Dong-chun(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Shenyang Beichuang Medical Laboratory Co.,Ltd.,Shenyang 110000,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China;School of Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China;Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]沈阳北创医学检验所有限公司,辽宁沈阳110000 [3]沈阳药科大学制药工程学院,辽宁沈阳110016 [4]沈阳药科大学中药学院,辽宁沈阳110016 [5]上海中医药大学交叉科学研究院,上海201203

出　　处：《中国现代中药》2021年第7期1240-1244,共5页Modern Chinese Medicine

基　　金：辽宁省大学生创新创业训练计划项目(201810163094);辽宁省自然科学基金指导计划项目(20180550371,2019-ZD-0447)。

摘　　要：目的:采用羧酸酯酶1(hCE1)特异性化学发光探针D-荧光素甲基醚(DME),在人肝微粒体(HLM)体系中测定18种调血脂类中药及12种中药单体对hCE1活性的抑制作用。方法:在HLM体系中,取不同中药饮片70%乙醇提取物的乙酸乙酯萃取层(简称酯层)与残留水层及中药单体化合物,分别与hCE1特异性探针DME在37℃条件下共同孵育,通过测定探针底物代谢产物的相对光单位(RLU)值计算酶活力(Eres),判断提取物及中药单体对hCE1的抑制程度。结果:绿茶酯层、女贞子水层、干姜酯层、甘草次酸、胡椒水层、决明子水层、红花酯层、决明子酯层、柴胡水层、制何首乌水层、胡椒酯层、蒲黄酯层对hCE1有较强的抑制作用(Eres<20%),质量浓度为20μg·mL–1时hCE1酶活力分别为0.35%、0.89%、3.69%、5.26%、5.64%、6.34%、7.79%、12.04%、13.70%、15.35%、16.66%、18.89%。结论:绿茶、女贞子、干姜、甘草、胡椒、决明子、红花、柴胡、制何首乌、蒲黄中的化学成分对hCE1有较强的抑制作用。服用这些药物或食物,如饮茶时,需要注意其羧酸酯酶抑制作用会影响hCE1参与代谢的药物的血药浓度及药效。Objective:To investigate inhibitory effects of extracts from 18 lipid-lowering Chinese medicinal materials and 12 Chinese medicinal materials-derived monomers on human carboxylesterase 1(hCE1)activity in the human liver microsome(HLM)system by hCE1-specific chemiluminescent probe D-luciferin methyl ester(DME).Methods:The ethyl acetate fraction(EAF)and the residual aqueous fraction(AQF)from 70%ethanol extracts of different Chinese medicinal materials were prepared for testing.In the HLM system,the above samples and monomers were incubated with DME at 37℃respectively.The relative light unit(RLU)of the probe substrate metabolite was measured to calculate the enzyme activity(Eres),by which the inhibitory effects of extracts and monomers of Chinese medicinal materials on hCE1 were assessed.Results:The EAFs of green tea,Zingiberis Rhizoma,Carthami Flos,Cassiae Semen,Piperis Fructus,and Typhae Pollen,AQFs of Ligustri Lucidi Fructus,Piperis Fructus,Cassiae Semen,Bupleuri Radix,and Polygoni Multiflori Radix Praeparata,and glycyrrhetinic acid showed strong inhibitory effects on hCE1(E_(res)<20%),with E_(res) of 0.35%,0.89%,3.69%,5.26%,5.64%,6.34%,7.79%,12.04%,13.70%,15.35%,16.66%,and 18.89%when the concentration was 20μg·mL^(-1).Conclusion:The chemical components from green tea,Ligustri Lucidi Fructus,Zingiberis Rhizoma,Glycyrrhizae Radix et Rhizoma,Piperis Fructus,Cassiae Semen,Carthami Flos,Bupleuri Radix,Polygoni Multiflori Radix Praeparata,and Typhae Pollen have strong inhibitory activities against hCE1.These drugs and food should be taken(such as drinking tea)with caution since their inhibitory effects on carboxylesterases may affect the plasma concentration and efficacy of the drugs involved in the metabolism of hCE1.

关 键 词：羧酸酯酶1 D-荧光素甲基醚 高脂血症 人肝微粒体 用药安全 

分 类 号：R285.[医药卫生—中药学]