# Anti-inflammatory and antioxidant effects of dipotassium glycyrrhizinate in acute respiratory distress syndrome

## TL;DR

This study shows that dipotassium glycyrrhizinate reduces inflammation and oxidative stress in a model of acute respiratory distress syndrome, suggesting it could be a promising natural treatment.

## Contribution

The study demonstrates DG's therapeutic potential in ARDS through in vitro, in vivo, and computational approaches.

## Key findings

- DG reduced ROS and pro-inflammatory cytokines in A549 cells and improved antioxidant activity.
- DG treatment in mice lowered inflammatory markers and improved lung tissue damage in an ARDS model.
- Network pharmacology and simulations revealed DG's interaction with key ARDS-related proteins and pathways.

## Abstract

Acute respiratory distress syndrome (ARDS) is a severe clinical syndrome driven by inflammation, oxidative stress, and pulmonary tissue injury, for which effective therapy drugs remain lacking. In this study, the therapeutic potential and underlying mechanisms of dipotassium glycyrrhizinate (DG) in ARDS were systematically evaluated through both in vitro and in vivo experiments.

In an A549 cell model, DG exhibited no cytotoxicity within the tested concentration range and significantly suppressed LPS-induced excessive reactive oxygen species (ROS) generation and pro-inflammatory cytokine expression, including Tumor necrosis factor (TNF)-α,and Interleukin (IL)-6, while upregulating the anti-inflammatory cytokine IL-10, indicating its potent anti-inflammatory and antioxidant properties. In an LPS-induced ARDS mouse model, DG treatment not only significantly reduced serum levels of inflammatory cytokines but also increased the activity of the antioxidant enzyme superoxide dismutase (SOD), decreased the levels of myeloperoxidase (MPO) and malondialdehyde (MDA), and markedly alleviated pulmonary histopathological damage, demonstrating notable tissue-protective effects. Based on these findings, network pharmacology analysis revealed that DG targeted multiple ARDS-related core proteins (EGFR, MAPK1, FGFR1) enriched in key signaling pathways such as PI3K-AKT, EGFR, and HIF-1. Molecular docking and molecular dynamics simulations further confirmed the stable binding and strong affinity between DG and EGFR, supporting a regulatory mechanism in the context of ARDS pathogenesis.

In conclusion, DG alleviates ARDS-associated inflammation and oxidative stress through coordinated modulation of multiple signaling pathways, providing a theoretical and experimental foundation for its potential development as a natural therapeutic agent against ARDS.