GNF (Novartis) , San Diego, CA , USA and.
Drug Metab Rev. 2015 Feb;47(1):12-20. doi: 10.3109/03602532.2014.990032. Epub 2014 Dec 16.
Herbal supplements are often regarded as "natural", and are, therefore, considered by many to be safer than pharmaceuticals; however, the adverse effects of these supplements are under-reported in many cases. Many herbal supplements, such as pyrrolizidine alkaloids, kava, chaparral and germander, are known to induce liver injury, which, in general, is one of the main toxicity liabilities observed in the clinic and accounts for about half of total liver failures. One example is the hepatotoxicity of pennyroyal oil, which is ingested as an abortifacient, among other uses. For three decades, the late Professor Sidney Nelson contributed to our understanding of the mechanism of toxicity of pennyroyal and broadened our understanding of chemical toxicology. Here we present the studies and review the findings on acute hepatotoxicity of pennyroyal oil. These studies involved the isolation and characterization of pennyroyal components, determination of the appropriate animal models, identification of the structural requirement for toxicity and determination of the target enzymes and the enzymes involved in the process of bioactivation. Studies with stable isotope labeled pennyroyal metabolites, pulegone and menthofuran, furthered our understanding of the role of cytochrome P450 in the oxidation of these compounds. This review presents the investigational tools used in the study of pennyroyal oil, allowing the reader to not only appreciate these methods but also utilize them to tackle and better understand metabolism-based toxicity in their own projects.
草药补充剂通常被认为是“天然的”，因此许多人认为它们比药物更安全；然而，在许多情况下，这些补充剂的不良反应报告不足。许多草药补充剂，如吡咯里西啶生物碱、卡瓦、白毛茛和甘菊，已知会引起肝损伤，一般来说，这是临床上观察到的主要毒性负债之一，约占总肝衰竭的一半。例如，作为堕胎药等用途的薄荷油就具有肝毒性。三十年来，已故的 Sidney Nelson 教授为我们理解薄荷油的毒性机制做出了贡献，并拓宽了我们对化学毒理学的理解。在这里，我们展示了关于薄荷油急性肝毒性的研究和综述。这些研究涉及薄荷成分的分离和表征、确定适当的动物模型、鉴定毒性的结构要求以及确定靶酶和生物活化过程中涉及的酶。使用稳定同位素标记的薄荷油代谢物，如薄荷酮和薄荷呋喃的研究进一步加深了我们对细胞色素 P450 在这些化合物氧化中的作用的理解。本综述介绍了研究薄荷油时使用的研究工具，使读者不仅能够欣赏这些方法，还能够利用它们来解决和更好地理解自己项目中的基于代谢的毒性。
