College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Department of Pharmacy, Hezhou City People's Hospital, Hezhou 542800, PR China.
J Ethnopharmacol. 2018 Jan 10;210:242-253. doi: 10.1016/j.jep.2017.06.027. Epub 2017 Jun 23.
The dried ripe seeds of Nux Vomica (Strychnos nux-vomica L.), a traditional Chinese medicine, have been used to treat multifarious symptoms. However, the clinical applications of Nux Vomica are limited by its severe toxicity. In this study, Nux Vomica was subjected to nuclear magnetic resonance (NMR) metabonomics and pathological examination to determine relevant biomarkers in target organs and to explain the underlying toxicity mechanism.
Thirty-six male Sprague-Dawley rats were randomly divided into three groups of twelve rats. The control group was oral gavaged with distilled water, and two experiment groups were treated with Nux Vomica at a dose of 0.315 and 0.630g/kg body weight. On days 14 and 21, serum, urine, liver and kidney tissues were collected for histopathological examination, biochemical analysis and H-NMR analysis.
The metabolites changes of rats treated with Nux Vomica are obviously differ from that of controls. In serum, low-dose group compared with control shows the significantly changes included elevated concentration of glucose, TMAO, and creatine, with decreased lipids, 3-HB, lactate, and unsaturated fatty acid. Change in taurine was only observed in the separation comparison of high-dose group and control. In urine, the variation metabolites included elevations in glucose, creatine, and TMAO as well as decreased lactate, succinate, α-ketoglutaric acid, citrate and hippurate in low-dose group compared with control. Only alanine and creatine were decreased significantly in high-dose group compared with control.
Nux Vomica induced disruptions in glycolysis, lipid and amino acid metabolism, and toxic effects were aggravated in liver and kidney tissues as dosing time was prolonged. H NMR-based metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of Nux Vomica decoction that caused liver and kidney injuries in rats.
作为一种传统中药，鸡矢藤（Strychnos nux-vomica L.）的干成熟种子已被用于治疗多种症状。然而，鸡矢藤的临床应用受到其严重毒性的限制。在本研究中，鸡矢藤采用核磁共振（NMR）代谢组学和病理检查来确定靶器官中的相关生物标志物，并解释潜在的毒性机制。
36 只雄性 Sprague-Dawley 大鼠随机分为三组，每组 12 只。对照组口服蒸馏水，实验组分别以 0.315 和 0.630g/kg 体重的剂量给予鸡矢藤。在第 14 天和第 21 天，收集血清、尿液、肝和肾组织进行组织病理学检查、生化分析和 H-NMR 分析。
鸡矢藤处理的大鼠代谢物变化明显不同于对照组。在血清中，与对照组相比，低剂量组的葡萄糖、TMAO 和肌酸浓度升高，脂质、3-HB、乳酸和不饱和脂肪酸浓度降低。仅在高剂量组与对照组的分离比较中观察到牛磺酸的变化。在尿液中，与对照组相比，低剂量组的变化代谢物包括葡萄糖、肌酸和 TMAO 的升高，以及乳酸、琥珀酸、α-酮戊二酸、柠檬酸和 hippurate 的降低。与对照组相比，仅在高剂量组中观察到丙氨酸和肌酸显著降低。
随着给药时间的延长，鸡矢藤会导致糖酵解、脂质和氨基酸代谢紊乱，并加重肝、肾组织的毒性作用。基于 NMR 的代谢组学结合生化和组织病理学方法可用于阐明导致大鼠肝、肾损伤的鸡矢藤汤的毒性机制。
