Institute of Traditional Chinese Medicine , Tianjin University of Traditional Chinese Medicine , Tianjin 300193 , China.
Key Laboratory of Formula of Traditional Chinese Medicine, Ministry of Education , Tianjin University of Traditional Chinese Medicine , Tianjin 300193 , China.
Chem Res Toxicol. 2018 Sep 17;31(9):852-860. doi: 10.1021/acs.chemrestox.8b00082. Epub 2018 Aug 22.
Psoralen is the main active component of Psoralea corylifolia and is used as a marker to assess its quality. The effects of psoralen on animals have been well characterized. However, the molecular pathway of its toxicity is not fully understood. In this study, the toxic effects of psoralen administration (60 mg/kg) for 7 days in Sprague-Dawley rats were observed. Serum biochemistry and liver histopathology were further investigated. Proton nuclear magnetic resonance was applied to characterize the metabolic profile of liver toxicity induced by psoralen and to find changed metabolites in rat serum and liver. It was revealed that visceral coefficients and serum biochemistry indexes were significantly changed in rats with psoralen-induced liver injury. Furthermore, the histopathological examination exhibited that the liver might be the target organ for psoralen. Metabolic analysis of both serum and liver samples further proved the liver was the target of toxicity of psoralen. Multivariate analysis identified 7 metabolites in serum samples and 15 in liver samples as potential biomarkers in liver injury induced by psoralen. In addition, our results suggest that psoralen can cause a disturbance in amino acid metabolism, especially valine, leucine, and isoleucine biosynthesis in both serum and liver samples. In conclusion, we combined the results of toxicity and metabolomics induced by psoralen and provide useful information about the safety and potential risks of psoralen and Psoralea corylifolia.
补骨脂素是补骨脂的主要活性成分，被用作评估其质量的标志物。补骨脂素对动物的影响已得到很好的描述。然而，其毒性的分子途径尚未完全了解。在这项研究中，观察了补骨脂素（60mg/kg）连续给药 7 天对 Sprague-Dawley 大鼠的毒性作用。进一步研究了血清生化和肝脏组织病理学。应用质子核磁共振波谱法对补骨脂素诱导的肝毒性的代谢谱进行了特征描述，并找到了大鼠血清和肝脏中发生变化的代谢物。结果表明，补骨脂素诱导的肝损伤大鼠的内脏系数和血清生化指标均发生显著变化。此外，组织病理学检查显示肝脏可能是补骨脂素的靶器官。对血清和肝脏样本的代谢分析进一步证明了肝脏是补骨脂素毒性的靶器官。多元分析在血清样本中鉴定出 7 种代谢物，在肝脏样本中鉴定出 15 种代谢物，它们可能是补骨脂素诱导肝损伤的生物标志物。此外，我们的结果表明，补骨脂素可以引起氨基酸代谢紊乱，特别是血清和肝脏样本中的缬氨酸、亮氨酸和异亮氨酸生物合成紊乱。总之，我们结合了补骨脂素引起的毒性和代谢组学结果，为补骨脂素和补骨脂的安全性和潜在风险提供了有用的信息。
