李晓静 严东明 冯琴 胡义扬

摘要 栀子苷及京尼平是我国首批药食两用药材栀子的主要成分，具有广泛的药理活性和临床应用价值，在长期临床应用中尚未见到严重的不良事件报道。但是近年来的动物实验及细胞实验报道栀子苷有剂量依赖的肝毒性，且其体内衍生物京尼平较栀子苷的毒性效应更甚。现从栀子苷及京尼平的结构、体内代谢、动物实验中的肝毒性效应，栀子苷及京尼平通过选择性抑制CYP450酶系、诱导过氧化损伤、诱导肝实质细胞凋亡、影响胆红素代谢及胆汁酸合成与运输从而产生肝损伤等方面进行总结，并提出人和动物之间是否存在毒性反应差异等问题，以期临床关注栀子的安全性评价，促进其进一步的深入研究。

关键词 栀子;栀子苷;衍生物;京尼平;动物;剂量依赖;肝毒性;毒理

Research Advances on the Mechanism of Hepatotoxicity of Geniposide and Genipin in Animals

LI Xiaojing1，YAN Dongming2，FENG Qin1，HU Yiyang1，2

（1 Shuguang Hospital & Institute of Hepatology，Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China; 2 Clinical Research Center，Institute of Clinical Pharmacology，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China）

Abstract Geniposide and genipin are the main components of the first batch of medicinal and edible medicinal herb gardenia in China，which have extensive pharmacological activity and clinical application value.No serious adverse events have been reported in long-term clinical application.Recently，however，animal experiments and cell experiments have reported that geniposide has dose-dependent hepatotoxicity，and the toxicity of its derivative ginipin is worse than that of geniposide.In this paper，we will review the structure of geniposide and genipin，their metabolism，liver toxicity effects in animal experiments.Geniposide and Genipin can through selectively restrain CYP450 enzyme system，induce oxidative damage and hepatocyte apoptosis，effect the bilirubin metabolism，bile acid synthesis and transportation so as to causing liver damage，and we also put forward some problems such as whether exists different toxic reaction between people and animals，in order to draw clinical attention to the safety evaluation of gardenia，and promote further in-depth study.

Keywords Gardenia; Geniposide; Derivatives; Kineping; Animals; Dose dependent; Liver toxicity; Toxicology

中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.17.026

梔子苷是中药栀子中活性成分最高的环烯醚萜苷类化合物，京尼平是栀子苷的苷元，也是栀子苷在体内经肠道代谢的产物。栀子广泛应用于临床，具有保肝利胆、抗炎镇痛的治疗作用[1]。现代药理学研究显示，栀子苷及体内代谢产物京尼平在降压、降糖、降脂、抗氧化、抗肿瘤、促进胰腺分泌、胃功能保护等方面具有一定活性，对四氯化碳、乙醇、黄曲霉素B1导致的肝损伤有保护作用，对神经系统和心脑血管系统疾病也有治疗作用[2]。虽然在临床广泛使用的含有栀子苷的中药制剂并没有见到严重的不良事件报道，但是许多动物实验及体外实验显示栀子苷及京尼平有一定的肝毒性。……