Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

IF 4.7 4区医学 Q1 CHEMISTRY, MEDICINAL Chinese Herbal Medicines Pub Date : 2024-01-01 DOI:10.1016/j.chmed.2023.10.002

Gang Feng , Jianli Bi , Wenfang Jin , Qi Wang , Zhaokui Dan , Baolei Fan

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Abstract

Objective

Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (¹H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored.

Methods

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 ¹H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.

Results

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.

Conclusion

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.

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基于药代动力学和代谢组学的大黄和大戟对肝脏保护机制的影响

目的基于高效液相色谱-质谱（HPLC-MS/MS）和氢核磁共振波谱（1H NMR）的代谢组学技术，探讨大黄、大戟联合RhRR对急性肝损伤的药代动力学特征和治疗机制。方法建立急性肝损伤模型，采用 HPLC-MS/MS 方法测定 RhRR-EuS 五种成分在大鼠体内的药代动力学方法。结果药代动力学结果显示，RhRR-EuS和RhRR在不同组别中存在不同程度的双峰现象，RhRR中游离蒽醌与EuS相容后吸收增加。此外，大鼠急性肝损伤的病理状态可选择性地促进大黄素、金丝桃醇、黄柏醇和芦荟大黄素的吸收。通过对急性肝损伤小鼠肝组织中 15 种差异代谢产物的研究发现，RhRR-EuS 和 RhRR 可通过调节谷氨酰胺和谷氨酸、丙氨酸、天门冬氨酸和谷氨酸以及磷脂的代谢来保护肝损伤。结论首次研究了RhRR-EuS和RhRR在急性肝损伤大鼠和小鼠体内的药代动力学和代谢组学差异，为DHZCP临床治疗肝病提供理论参考。

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