# Cellular Metabolomics Reveals Differences in the Scope of Liver Protection Between Ammonium-Based Glycyrrhizinate and Magnesium Isoglycyrrhizinate

## TL;DR

This study compares how two liver-protecting drugs, diammonium and magnesium isoglycyrrhizinate, work differently at the cellular level to protect the liver.

## Contribution

The study provides new insights into the distinct mechanisms and clinical applications of diammonium and magnesium isoglycyrrhizinate in liver protection.

## Key findings

- MAGN enhances antioxidant components, making it suitable for drug-induced liver injury.
- DIAM is more effective for non-alcoholic fatty liver disease and viral hepatitis.
- Both DIAM and MAGN show better bioavailability and liver protection than monoammonium glycyrrhizinate.

## Abstract

Background: Despite the well-established liver-protective efficacy of monoammonium glycyrrhizinate (MONO), diammonium glycyrrhizinate (DIAM), and magnesium isoglycyrrhizinate (MAGN), which has been translated into clinical practice, their clinical differentiation remains elusive owing to their structural similarities and overlapping therapeutic effects. Methods: The present study delves into the pharmacokinetics, cellular-level liver-protective potencies, and underlying mechanisms of action of these three compounds through a comprehensive analysis. Results: The findings reveal that both DIAM and MAGN exhibit superior bioavailability and hepatoprotective profiles compared to MONO. Notably, an investigation of the metabolic pathways mediating liver protection in normal human liver cells (LO2), utilizing an ultra-performance liquid chromatography–time of flight tandem mass spectrometry (UPLC-TOF-MS/MSe) platform, demonstrated that MAGN augments antioxidant components, thereby favoring its application in drug-induced liver injury (DILI). Conversely, DIAM appears to be a more suitable candidate for addressing non-alcoholic fatty liver disease (NAFLD) and viral hepatitis. Conclusion: This study contributes novel perspectives on the mechanisms of action and potential clinical utilities of DIAM and MAGN in liver disease prevention and management.