Integrated metabolomics and transcriptomics to study mechanisms of Paecilomyces cicadae-fermented Radix astragali in the treatment of hyperuricemia

The prevalence of hyperuricemia (HUA) is rising annually due to societal growth and changes in lifestyle. Bidirectional solid-state fermentation of substrates has demonstrated encouraging uses in the clinical treatment of HUA. To investigate the powerful therapeutic potential of solid-state fermentation products of Radix astragali and Paecilomyces cicadidae (RPF), multi-omics analysis was applied. Spearman analysis between serum biomarkers and differential expressed genes (DEGs) was used to estimate the potential mechanism of RPF against HUA, which was induced by high purine diet (HPD) and potassium oxonate. This study found that the serum uric acid, triglycerides, glucose, and creatinine level were decreased in HUA rats after RPF treatment. In addition, RPF effectively attenuated renal inflammation and lipid accumulation in the livers. Untargeted metabolomics and transcriptome sequencing technology demonstrated that the pathway regulated by RPF were "caffeine metabolism", "fatty acid biosynthesis", and "AMPK signaling". Moreover, the correlation demonstrated that metabolites (allantoin, pyridoxamine, cytidine, cortodoxone, corticostrone) and DEGs (Phald3, Ccdc80) showed significantly positive correlations under RPF influence. Overall, findings of current study indicated the interactions between serum metabolites and renal genes. In line with these findings, the mechanism of the anti-HUA effect of RPF was revealed. In summary, the current study suggest pharmacological support for treating HUA with RPF.