Feng Gang, Bi Jianli, Jin Wenfang, Wang Qi, Dan Zhaokui, Fan Baolei
The First People's Hospital of Xianning, Xianning 437000, China.
Hubei University of Science and Technology, Xianning 437100, China.
Chin Herb Med. 2023 Dec 18;16(1):121-131. doi: 10.1016/j.chmed.2023.10.002. eCollection 2024 Jan.
Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (H NMR), the pharmacokinetic characteristics and therapeutic mechanism of et (RhRR, Dahuang in Chinese), (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored.
Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.
Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS.
For the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.
基于高效液相色谱 - 质谱联用(HPLC - MS/MS)和氢核磁共振波谱(¹H NMR)的代谢组学技术,探讨大黄(RhRR)、土鳖虫(EuS)及其配伍对急性肝损伤的药代动力学特征及治疗机制。
建立急性肝损伤模型,采用HPLC - MS/MS法研究大黄 - 土鳖虫复方中5种成分在大鼠体内的药代动力学。采用¹H NMR波谱结合多元统计分析方法对不同组小鼠肝组织进行分析,研究大黄 - 土鳖虫复方及大黄的代谢组学。
药代动力学结果显示,不同组均有不同程度的双峰现象,大黄与土鳖虫配伍后大黄中游离蒽醌的吸收增加。此外,大鼠急性肝损伤病理状态可选择性促进大黄素、大黄酚、大黄素甲醚和芦荟大黄素的吸收。通过急性肝损伤小鼠肝组织中的15种差异代谢物,揭示大黄 - 土鳖虫复方及大黄可通过调节谷氨酰胺与谷氨酸、丙氨酸、天冬氨酸与谷氨酸以及磷酸肌醇的代谢来保护肝损伤。然而,大黄的调节作用弱于大黄 - 土鳖虫复方。
首次研究大黄 - 土鳖虫复方及大黄在急性肝损伤大鼠和小鼠中的药代动力学及代谢组学差异,为临床应用大黄蛰虫胶囊治疗肝病提供理论参考。