# Elucidating the Mechanism of Liver and Kidney Damage in Rats Caused by Exposure to 2,4-Dichlorophenoxyacetic Acid and the Protective Effect of Lycium barbarum Polysaccharides Based on Network Toxicology and Molecular Docking

## TL;DR

This study explores how a common herbicide harms rat liver and kidney, and how a natural compound from Lycium barbarum can protect against this damage.

## Contribution

The study introduces a novel multi-target protective mechanism of Lycium barbarum polysaccharides against 2,4-D-induced organ damage using network toxicology and molecular docking.

## Key findings

- 2,4-D caused significant liver and kidney damage in rats through oxidative stress and apoptosis.
- Lycium barbarum polysaccharides significantly reduced oxidative stress and tissue damage in treated rats.
- Network analysis identified key targets like PPARG and NFE2L2 involved in the protective effects of Lycium barbarum polysaccharides.

## Abstract

2,4-Dichlorophenoxyacetic acid (2,4-D) is a widely used herbicide, yet its potential to induce hepatorenal injury via oxidative stress and apoptosis raises significant health concerns. Lycium barbarum polysaccharides (LBP) possess recognized antioxidant and anti-apoptotic properties, but their protective mechanisms against 2,4-D toxicity, particularly through a multi-target network, remain inadequately explored. This study aimed to systematically investigate the mechanisms of 2,4-D-induced hepatorenal injury and the protective efficacy of LBP by integrating network toxicology, molecular docking, and experimental validation. An integrated approach was employed. Core targets and pathways were identified via network toxicology. Molecular docking predicted interactions between 2,4-D and these targets. In vivo validation was conducted on Sprague-Dawley rats treated with 2,4-D (75 mg/kg) and/or LBP (50 mg/kg) for 28 days, assessing histopathology, serum oxidative stress markers superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and cellular apoptosis (TUNEL staining). Network analysis identified PPARG, NFKB1, PPARA, NFE2L2, and SERPINE1 as core targets, with molecular docking confirming strong binding affinities (binding energies: −5.1 to −6.3 kcal·mol−1) and KEGG enrichment implicating cAMP, Ca2+, and PPAR signaling pathways. Experimentally, 2,4-D exposure induced significant histopathological damage, suppressed SOD/GSH-Px activities (p < 0.001), elevated MDA levels (p < 0.001), and markedly increased renal apoptosis (p < 0.01). Crucially, LBP intervention substantially mitigated these alterations, ameliorating tissue injury, restoring antioxidant defenses, increasing SOD/GSH-Px (p < 0.01), reducing MDA (p < 0.001) and significantly decreasing renal apoptosis (p < 0.05). This study elucidates a multi-target mechanism for 2,4-D-induced hepatorenal injury centered on oxidative stress–apoptosis dysregulation and demonstrates that LBP confers significant protection likely via modulation of this network. These findings underscore the potential of LBP as a natural protective agent against pesticide-induced organ damage and highlight the utility of integrated network approaches in toxicological research.