Institute for Tibetan Medicine, China Tibetology Research Center, Beijing, 100101, China.
Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
J Pharm Biomed Anal. 2019 Nov 30;176:112800. doi: 10.1016/j.jpba.2019.112800. Epub 2019 Aug 1.
The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.
雪兔子（Herpetospermum caudigerum Wall）是一种传统的藏药，在临床实践中被广泛应用。然而，雪兔子的外壳（SHCW）很少被研究过，一些研究人员认为 SHCW 可能具有毒性。因此，在这项研究中，SHCW 以 0.1 和 0.33 g/kg 的两个剂量每天一次给药大鼠，持续 21 天。首次通过基于 H-NMR 的代谢组学结合组织病理学观察和生化检测研究了 SHCW 对大鼠肝脏的刺激作用。组织病理学切片显示，给药组大鼠的肝组织中存在一定程度的肝细胞水肿和肝窦充血。血清生化指标显示 ALT、AST 和 MDA 显著升高，SOD 显著降低。代谢组学结果表明，大鼠灌胃给予 SHCW 提取物后其代谢物发生了变化。通过多变量统计分析和单变量分析发现，SHCW 可导致大鼠能量代谢、氧化应激和氨基酸代谢紊乱，进而导致肝损伤。这种综合的代谢组学方法证明了它能够描述生物体的整体代谢状态，并为探索药物引起的毒性或副作用提供了一种强大而可行的工具。
