PROTECTIVE EFFECTS OF A RODGERSIA SAMBUCIFOLIA FLAVONOID–SCUTELLARIA POLYSACCHARIDE COMPOUND AGAINST PSEUDORABIES VIRUS-INDUCED TESTICULAR INJURY VIA MODULATION OF THE FOXO SIGNALING PATHWAY - Jianqin Li; Ying Zhang; Junyi Lin; Jiajia Wei; Chunlian Song; Xianghua Shu (Journal of Animal and Plant Sciences, 2026)
Pseudorabies virus (PRV) is known to induce severe reproductive disorders, yet the underlying molecular mechanisms responsible for testicular damage remain incompletely elucidated. This research aims to explore the impact of PRV infection on porcine testicular (ST) cells and murine testicular tissue, with a focus on the involvement of the FOXO signaling pathway. Meanwhile, evaluate the antagonistic effect of compound RS on PRV infection by regulating this pathway. Analyze differentially expressed genes and enriched pathways in ST cells infected with PRV through transcriptome sequencing. ST cells infected with PRV were treated with FOXO pathway inhibitor (AS1842856) and different concentrations of RS. Cell viability was detected by CCK-8, viral load and mRNA expression of FOXO were detected by qPCR. Establish a PRV infected mouse model, observe pathological changes in testicular tissue through HE staining, detect testicular virus concentration, sperm count, and FOXO gene expression. PRV infection causes significant cytopathic effects in ST cells, leading to upregulation of 1650 genes and downregulation of 1359 genes. KEGG pathway analysis indicated significant enrichment of these genes in the FOXO signaling pathway, among others. Inhibition of the FOXO pathway markedly reduced viral replication in ST cells.PRV infection upregulated FOXO1 and FOXO4 mRNA expression, while downregulating FOXO3; these alterations were reversed upon RS treatment. In vivo experiments, RS treatment alleviated the pathological damage of mouse testicular tissue caused by PRV, reduced virus concentration in the testes, and partially restored sperm count. Compound RS effectively suppresses PRV replication both in vitro and in vivo by modulating the FOXO pathway and alleviates testicular injury caused by PRV. These findings offer a theoretical foundation and suggest a promising candidate for developing novel therapeutics targeting PRV-associated reproductive toxicity.
Keywords: journal article; Rodgersia sambucifolia hemsl flavon; Scutellaria polysaccharide; Pseudorabies virus; FOXO signaling