Protective effect of astragalus polysaccharides against sodium fluoride-induced liver injury: A comprehensive study based on network pharmacology, metabolomics, and transcriptomics

Fluoride, a water-soluble environmental contaminant, poses significant risks to hepatic health due to long-term excessive intake, yet effective interventions for NaF-induced liver injury remain limited. Astragalus polysaccharides (APS), the principal bioactive component of Astragalus membranaceus, exhibit immunomodulatory, anti-inflammatory, and antioxidant properties, and have been shown to protect against alcohol- and chemical-induced liver injury. This study employed animal experiments and integrative multi-omics (network pharmacology, transcriptomics, metabolomics) to investigate the protective mechanisms of APS against NaF toxicity in rats. Results showed APS alleviated growth retardation, reduced liver index and serum ALT/AST levels, and enhanced antioxidant capacity. Transcriptomics and metabolomics results revealed that APS reversed 1378 differentially expressed genes and 48 metabolites, significantly improving inflammatory and lipid metabolic disorders. Multi-omics integrated analysis demonstrated that APS may alleviate NaF-induced liver injury in rats through a multi-target and multi-pathway mechanism, specifically possibly related to the NF-κB/AGE-RAGE/Th17 inflammatory pathway, activation of the PPAR lipid metabolism pathway, and upregulation of detoxification-related genes Cyp2e1 and Gsta1. These findings establish a molecular basis for the potential use of APS in treating NaF-induced liver injury and contribute to the understanding of the protective effects of traditional Chinese medicine polysaccharides.