药学学报, 2019, 54(3): 420-431
引用本文:
汤俊, 程敏. 紫草中的吡咯里西啶类成分及其代谢毒性研究进展[J]. 药学学报, 2019, 54(3): 420-431.
TANG Jun, CHENG Min. Recent progress in the research on pyrrolizidine alkaloids from Chinese medicinal herb “Zicao” and their metabolic toxicity[J]. Acta Pharmaceutica Sinica, 2019, 54(3): 420-431.

紫草中的吡咯里西啶类成分及其代谢毒性研究进展
汤俊1, 程敏2
1. 武汉大学药学院, 组合生物合成与新药发现教育部重点实验室, 湖北 武汉 430071;
2. 武汉药品医疗器械检验所, 湖北 武汉 430075
摘要:
吡咯里西啶生物碱(pyrrolizidine alkaloids,PAs)是植物中较常见的一类肝毒性成分。紫草为我国常用中药之一,因具有抗炎、促进伤口愈合等作用而广泛应用于临床,但研究表明含有PAs。这类成分在体内大量暴露及代谢活化可致肝窦阻塞综合征,故被认为是许多含PAs中草药引起肝损伤作用的潜在物质基础。尽管有关紫草的临床毒害未见报道,但PAs的存在无疑为其安全用药埋下了隐患,揭示和控制其毒性风险已成为紫草研究的一个重要方向。本文拟从吡咯里西啶类成分及其代谢毒性两个方面对紫草及其相关品种的安全性研究进展及存在的主要问题做一概述,并对进一步的研究提出建议,以期为全面系统评价紫草的用药风险和指导其临床合理用药提供参考。
关键词:    紫草      吡咯里西啶生物碱      代谢毒性      药源性肝损伤      安全性评价     
Recent progress in the research on pyrrolizidine alkaloids from Chinese medicinal herb “Zicao” and their metabolic toxicity
TANG Jun1, CHENG Min2
1. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China;
2. Wuhan Institute for Drug and Medical Device Control, Wuhan 430075, China
Abstract:
Pyrrolizidine alkaloids (PAs) are a class of hepatotoxic compounds that are largely found in plants. "Zicao" is one of the most commonly-used Chinese herbal medicines from multiple sources, owing to its anti-inflammatory and wound healing effects. However, many studies have shown that this herb and its relative species contain hepatotoxic PAs. These PAs may cause hepatic sinusoidal obstruction syndrome following metabolic activation, and are therefore considered as potential toxic substances. Even though the toxicity of "Zicao" in clinical use has not been reported, the existence of PAs will undoubtedly post a threat for its safety in long-term use. It has now become the focus of many researchers to disclose and prevent its potential risk of intoxication. This review summarizes recent progress and key scientific evidence found in the research of pyrrolizidine alkaloids from "Zicao" and its relative species, including their metabolic toxicity. We comment on the need of future studies, such as providing a reference or guidance for safety evaluation of this medicinal herb in clinical practice.
Key words:    Zicao    pyrrolizidine alkaloid    metabolic toxicity    drug-induced liver injury    safety evaluation   
收稿日期: 2018-09-21
DOI: 10.16438/j.0513-4870.2018-0870
基金项目: 国家自然科学基金面上项目(31270401);湖北省食品药品监督管理局科研项目(201601021).
通讯作者: 汤俊
Email: tangj0205@whu.edu.cn
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