Wu Huifei, Zhang Wenxia, Lin Hui, Ye Qiuming, Guo Jiayin, Quan Shijian
Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan 528400, China.
Guangdong Provincial Key Laboratory of Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Evid Based Complement Alternat Med. 2022 Sep 13;2022:6539675. doi: 10.1155/2022/6539675. eCollection 2022.
Fuzi is commonly used in traditional Chinese medicine. Clinical Fuzi poisoning cases have frequently been reported. Glycyrrhizae Radix is often used to alleviate Fuzi's toxicity. However, the poisoning mechanism of Fuzi and the detoxication mechanism of Glycyrrhizae Radix are still not clear. We identified the chemical components of Fuzi at different decoction times (0.5, 1, 2, 4, and 6 h) using ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. A total of 35 compounds were detected in the Fuzi decoction, including diester alkaloids, monoester alkaloids, amino acids, phenolic acids, organic acids, glycosides, and sugars among others. The content of diester alkaloids (i.e., subaconitine, neoaconitine, and aconitine) in the Fuzi decoction decreased after 2 h of decoction time, while the content of monoester alkaloids (i.e., benzoyl aconitine and benzoyl subaconitine) reached a peak at 2 h. A total of 32 rats were randomly divided into four groups, including 8 cases in the low-dosage Fuzi decoction group A, 8 cases in the high-dosage Fuzi decoction group B, 8 cases in the Fuzi and glycyrrhizae decoction group C, and 8 cases in the control group D. The decoction was administered orally for 7 days. Then, a serum was obtained. The metabolites' changes were analyzed in serum metabolomics using liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Statistical analysis and pathway analysis were used to assess the effects of glycyrrhizae on the metabolic changes induced by Fuzi. The behavioral and biochemical characteristics indicated that Fuzi exhibited toxic effects on rats and their metabolic profiles changed. However, the metabolic profiles of the glycyrrhizae group became similar to those of the control group. These profiles showed that glycyrrhizae can effectively improve Fuzi poisoning rats. Our study demonstrated that the established pseudotargeted metabolomics is a powerful approach for investigating the mechanisms of herbal toxicity.
附子是中医常用药物。临床附子中毒病例屡有报道。甘草常被用于减轻附子的毒性。然而，附子的中毒机制以及甘草的解毒机制仍不明确。我们采用超高效液相色谱四极杆飞行时间质谱法鉴定了附子在不同煎煮时间（0.5、1、2、4和6小时）的化学成分。在附子煎剂中总共检测到35种化合物，包括二酯生物碱、单酯生物碱、氨基酸、酚酸、有机酸、糖苷和糖类等。附子煎剂中二酯生物碱（即次乌头碱、新乌头碱和乌头碱）的含量在煎煮2小时后降低，而单酯生物碱（即苯甲酰乌头碱和苯甲酰次乌头碱）的含量在2小时达到峰值。总共32只大鼠被随机分为四组，低剂量附子煎剂组A有8只，高剂量附子煎剂组B有8只，附子与甘草煎剂组C有8只，对照组D有8只。连续7天口服给药煎剂。然后，采集血清。采用液相色谱 - 串联质谱法（UPLC - MS/MS）在血清代谢组学中分析代谢物的变化。使用统计分析和通路分析来评估甘草对附子诱导的代谢变化的影响。行为和生化特征表明附子对大鼠表现出毒性作用且其代谢谱发生改变。然而，甘草组的代谢谱与对照组相似。这些结果表明甘草能有效改善附子中毒的大鼠。我们的研究表明，所建立的准靶向代谢组学是研究草药毒性机制的有力方法。
