栀子苷及京尼平的动物肝毒性机制研究进展

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

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。

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.