栀子苷体内吸收、分布、代谢和排泄过程及其肝毒性研究进展  

Absorption,distribution,metabolism and excretion and the hepatotoxicity of geniposide:a research progress

作　　者：高爱 张文生[1,2,3] 冯成强 GAO Ai;ZHANG Wen-sheng;FENG Cheng-qiang(Engineering Research Center of Natural Medicine,Ministry of Education,Beijing Normal University,Beijing 100875,China;Beijing Key Laboratory of Traditional Chinese Medicine Protection and Utilization,Beijing Normal University,Beijing 100875,China;Zhuhai Branch of State Key Laboratory of Earth Surface Processes and Resource Ecology,Zhuhai 519087,China)

机构地区：[1]北京师范大学天然药物教育部工程研究中心,北京100875 [2]北京师范大学中药资源保护与利用北京市重点实验室,北京100875 [3]地表过程与资源生态国家重点实验室珠海基地,广东珠海519087

出　　处：《中国药理学与毒理学杂志》2022年第7期552-558,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81771152)。

摘　　要：栀子是我国首批公布的药食同源物,兼具临床药用和日常食用价值,应用前景广阔。但近年来多有文献报道其主要活性成分栀子苷具有肝毒性,这使得其安全性日益受到重视。栀子苷可通过胃肠道、皮肤、鼻腔吸入、肌肉注射和静脉注射等方式进入体内;进入体内后广泛分布在肾、脾、肝、心、肺和脑等器官中;在Ⅰ相反应阶段主要发生水解反应,京尼平是其主要水解产物,京尼平进一步与氨基、葡萄糖醛酸和磺酸基等发生Ⅱ相结合反应;栀子苷经过体内代谢后多以栀子蓝形式排出体外。对于栀子苷毒性参数研究多集中在半数致死剂量以及观察到有害作用的最低水平,尚未见文献报道其未观察到有害作用水平。栀子苷肝毒性效应表现为影响大鼠行为、肝指数增加、肝功能指标升高、肝细胞损害、胆汁淤积和影响肝窦状隙等,其肝损伤机制包括引发共价结合反应,影响代谢酶表达和活性,引起胆汁酸稳态失衡、氧化应激、炎症反应和肝细胞凋亡等。Gardenia jasminoodes Ellis is one of the first announced medicinal and food homologues in China,which is of both medicinal and edible value with good prospects.However,there have been many reports in that its main active aingredient geniposide has hepatotoxicity.Therefore,the safety of Gardenia jasminoodes Ellis has attracted more attention.Geniposide can be absorbed into the body through the gastrointestinal tract,skin,nasal inhalation,intramuscular injection or intravenous injection.Once in the body geniposide can be widely distributed in the kidney,spleen,liver,heart,lung and brain.Geniposide is metabolized to genipin through phaseⅠhydrolysis reaction,and genipin will further react with amino,glucuronic acid and sulfate group in phaseⅡcombination reaction.Geniposide is mostly excreted in the form of Gardenia Blue.As for the toxicity parameters of geniposide,most of the studies have focused on the LD50and the no observed adverse effect level,while the lowest observed adverse effect level has never been reported in literature.The hepatotoxic effects of geniposide are manifested as affecting the behavior of rats,increasing liver organ indexes,increasing liver function indexes,damaging liver cells,causing cholestasis,and affecting liver sinusoids.The mechanisms of liver injury includes triggering covalent binding reaction,affecting the expression and activity of metabolic enzymes,causing imbalance of bile acid homeostasis,oxidative stress,inflammatory response and hepatocyte apoptosis.

关 键 词：栀子苷 代谢 肝毒性 

分 类 号：R285.1[医药卫生—中药学] R969.1[医药卫生—中医学]