Investigating the protective role of Astragalus polysaccharides against fluoride-induced testicular injury via network pharmacology, molecular docking, and in vivo experiments.

OBJECTIVE

This study aimed to investigate the protective effects of Astragalus polysaccharides (APS) against sodium fluoride (NaF)-induced testicular damage and to provide a theoretical basis for developing natural strategies to mitigate fluoride-induced reproductive toxicity.

METHODS

Network pharmacology was employed to identify potential targets and pathways of APS in treating fluoride-induced testicular injury. Molecular docking was used to assess the binding affinity between APS active compounds and core targets. An in vivo rat model was established to evaluate testicular index, fluoride accumulation, and histopathological changes. Oxidative stress markers including SOD, CAT, GSH, and MDA were measured. Immunohistochemistry was performed to assess blood-testis barrier integrity and the expression of key targets (AKT1, ESR1, CASP3).

RESULTS

Network pharmacology identified 34 potential APS targets, enriched in apoptosis, PI3K-Akt, and IL-1B signaling pathways. Molecular docking revealed strong binding affinity of APS components to core targets. APS significantly improved NaF-induced reductions in testicular index (p < 0.01) and fluoride accumulation (p < 0.05), alleviated seminiferous tubule atrophy and mitochondrial swelling, enhanced SOD, CAT activities and GSH levels (p < 0.01), and reduced MDA levels (p < 0.01). Moreover, APS upregulated CLDN1, ZO-1, and Occludin expression to repair the blood-testis barrier. Abnormal expression of AKT1, ESR1, CASP3, and HSP90AA1 was reversed by APS (p < 0.01).

CONCLUSION

APS mitigates fluoride-induced testicular toxicity via multi-target regulation of oxidative stress and blood-testis barrier pathways, offering a novel therapeutic approach for fluoride-related reproductive damage.