藏药植物药内源性生物碱类毒性成分的代谢转化及减毒特征研究进展  

Metabolic transformation and attenuation characteristics of endogenous alkaloid toxic components of Tibetan medicinal herbs:a review

作　　者：王一妃 龚莹[2] 秦玲玲[2] 郭磊[2] 唐丽[1] 

机构地区：[1]中央民族大学生命与环境科学学院,北京100081 [2]军事医学科学院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《中国药理学与毒理学杂志》2017年第8期849-858,共10页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81373765);教育部新世纪优秀人才支持计划(NCET-12-0578);国家科技重大专项(2014ZX09304307001)~~

摘　　要：某些藏药植物药中的活性成分同时也是毒性成分,需要在使用中确切了解其作用机制及代谢途径。毒性较大的藏药植物药,其内源性毒性成分主要为生物碱,如乌头类、甲基牛扁碱等二萜生物碱、莨菪烷类生物碱、马钱子碱、士的宁、罂粟碱和苦马豆素等。藏药植物药中具有代表性的内源性生物碱类毒性成分多存在于根、种子和果实中,多因其剧毒或高毒化学物本质,表现出神经毒性和心脏毒性。一般经去烷基、羟基化和水解等Ⅰ相代谢过程及与葡萄糖醛酸、磺酸结合等Ⅱ相代谢过程,产生多种高极性和毒性减弱的代谢产物,排出体外。多种生物碱的中毒剂量与治疗剂量相近,藏药典籍中常采用炒制、奶制、青稞酒制和诃子配伍等减毒后入药。本文针对包括乌头类二萜双酯、莨菪烷和马钱子碱等在内的5类12种生物碱,着重评述其代谢转化、减毒和安全性评价特点,以期为制定藏药植物药内源性毒性成分限量、临床用药和减毒治疗提供全面参考。The active ingredients in some Tibetan medicinal herbs are toxic components as well, and we need to have a clear understanding of their mechanism and metabolic pathways in use. The endogenous toxic components of highly toxic Tibetan herbal medicines are mainly alkaloids, such as aconitum alkaloids, methyllycaconitine, tropane alkaloids, brucine, strychnine, papaverine and swainso- nine. The majority of endogenous toxic alkaloids in Tibetan medicine herbs exist in roots, fruits and seeds of plants, exerting neurotoxicity or cardiotoxicity as highly toxic inherent chemicals. Most alkaloids are metabolized in phase I via de-alkylation, hydroxylation, hydrolysis and other reactions, as well as in phase II via glucuronic acid and sulfonic acid conjugation. They form various metabolites with high polarities and reduced toxicities so as to be easily excreted. The closeness between the therapeutic dose and toxic dose of alkaloids components in Tibetan medicinal herbs leads to their attenuated preparation via frying, dairy, highland barley wine soaking, or in combination with Terminalia Chebula to decrease toxicity, as is cited classic books on in Tebitan medicine. Focused on twelve alkaloids of five classes including aconitine, tropane and brucine, we have reviewed the characteristics of their metabo- lism and transformation, as well as their toxicity attenuation and safety evaluation.

关 键 词：藏药植物药 内源性毒性成分 代谢转化 减毒 

分 类 号：R29[医药卫生—民族医学]