黄连水提液中木兰花碱和木兰花碱单体代谢动力学差异  

Differences of Metabolic Kinetics Between Monomeric Magnoflorine and Magnoflorine in Coptidis Rhizoma Water Extract

作　　者：薛宝娟[1,2] 汪祺 闫天月[1] 王雪 荆紫琪 张玉杰 马双成[3] XUE Bao-juan;WANG Qi;YAN Tian-yue;WANG Xue;JING Zi-qi;ZHANG Yu-jie;MA Shuang-cheng(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Monitoring and Statistical Research Center,National Administration of Traditional Chinese Medicine,Beijing 100027,China;National Institutes for Food and Drug Control,Beijing 100050,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]国家中医药管理局监测统计中心,北京100027 [3]中国食品药品检定研究院,北京100050

出　　处：《中国现代中药》2023年第1期73-82,共10页Modern Chinese Medicine

基　　金：国家自然科学基金项目(81673680)。

摘　　要：目的:探讨黄连水提液中木兰花碱和木兰花碱单体代谢动力学差异。方法:采用大鼠体外肠渗透液-肝微粒体温孵联动模型,考察木兰花碱体外肝微粒体代谢动力学特性,并采用高效液相色谱-线性离子阱/静电场轨道阱高分辨质谱法(HPLC-LTQ/Orbitrap MS)对木兰花碱代谢产物进行定性鉴别,分析木兰花碱代谢途径,考察木兰花碱与黄连中其他成分代谢性相互作用。结果:黄连水提液中木兰花碱的米氏常数[K_(m),(0.53±0.16)μmol·L^(-1)]低于木兰花碱单体[(0.85±0.12)μmol·L^(-1),P<0.05],表明黄连水提液中木兰花碱对大鼠肝微粒体的亲和性大于木兰花碱单体;黄连水提液组最大反应速度(V_(max))、肝固有清除率(CL_(int))及肝清除率(CL)均低于木兰花碱单体组(P<0.05),黄连水提液组半衰期(T_(1/2),44.22 min)较木兰花碱组(37.35 min)延长(P<0.01),表明黄连水提液中木兰花碱在大鼠肝微粒中代谢和消除速率变慢,T_(1/2)更长。木兰花碱与黄连水取液中木兰花碱的代谢产物存在差别。木兰花碱检出代谢产物5个,黄连水提液中检出木兰花碱的代谢产物8个。木兰花碱代谢途径主要为羟基化、去甲基化、脱氢、酮基化、葡萄糖化和葡萄糖醛酸化。黄连水提液中木兰花碱一羟基化代谢产物及一脱甲基化代谢产物在肝微粒体中可进一步发生羟基化代谢。结论:木兰花碱在肠道和肝微粒体中均可产生代谢。黄连中其他成分可降低木兰花碱在大鼠肝微粒体中的代谢速率,增加其代谢产物的数量。Objective:To investigate the differences in metabolic kinetics between monomeric magnoflorine and magnoflorine in Coptidis Rhizoma water extract.Methods:The linkage rat model of"intestinal penetrating fluid-liver microsome incubation"in vitro was adopted to study the metabolic kinetic characteristics of magnoflorine in vitro liver microsome and to identify the metabolites by high performance liquid chromatography-linear ion trap/electrostatic field orbitrap high resolution mass spectrometry(HPLC-LTQ/Orbitrap MS).The metabolic pathways of magnoflorine were analyzed,and the interaction between magnoflorine and coexisting components in Coptidis Rhizoma was investigated.Results:The Michaelis constant[K_(m),(0.53±0.16)μmol·L^(-1)]of magnoflorine in Coptidis Rhizoma water extract was lower than that[(0.85±0.12)μmol·L^(-1)]of magnoflorine monomer(P<0.05),which indicated that the affinity of magnoflorine in Coptidis Rhizoma water extract in the rat liver microsome was higher than that of magnoflorine monomer.The maximum reaction velocity(V_(max)),hepatic intrinsic clearance(CL_(int)),and hepatic clearance(CL)of magnoflorine in Coptidis Rhizoma water extract were lower than those of magnoflorine monomer(P<0.05),and the half-time(T_(1/2))of magnoflorine in Coptidis Rhizoma water extract(44.22 min)was higher than that(37.35 min)of magnoflorine monomer(P<0.01),suggesting that the metabolism and elimination rates of magnoflorine in Coptidis Rhizoma water extract in the rat liver microsome were slower,and the half-life period was longer.The results indicated that monomeric magnoflorine and magnoflorine in Coptidis Rhizoma water extract had different metabolites.Five metabolites were found in monomeric magnoflorine,while eight metabolites were found in magnoflorine in Coptidis Rhizoma water extract.The pathways to these metabolites were hydroxylation,demethylation,dehydrogenation,ketonization,glucosylation,and glucuronidation.Mono-hydroxylation and mono-demethylation metabolites of magnoflorine in Coptidis Rhizoma water e

关 键 词：木兰花碱 黄连 高效液相色谱-线性离子阱/静电场轨道阱高分辨质谱法 肠-肝代谢 代谢动力学 代谢产物 相互作用 

分 类 号：R285[医药卫生—中药学]