Ferulic acid supplementation alleviates hyperuricemia in high-fructose/fat diet-fed rats via promoting uric acid excretion and mediating gut microbiota

The prevalence of hyperuricemia (HUA) has been rising recently and it is usually accompanied by renal injury and intestinal flora disorder, leading to a nonnegligible health crisis. Ferulic acid (FA) as a familiar polyphenol has been proven to exert antihyperuricemic properties via inhibiting uric acid (UA) synthesis in the previous study, while the mechanisms remain not exhaustive. This work aimed at exploring the regulatory effect of FA on UA excretion, which is another strategy for UA lowering, and the comorbidities of HUA. Firstly, FA downregulated the gene expressions of urate absorption transporters and repressed the Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-kB) pathway in UA-stimulated HK-2 cells. Subsequently, FA or allopurinol was given to rats with HUA caused by high-fructose/fat diet (HFFD) for 20 weeks. FA markedly decreased the serum UA, blood urea nitrogen, and creatinine levels. Expressions of urate absorption transporters were downregulated and those of secretion transporters were upregulated in the kidney and intestine of HUA rats administered FA. Additionally, FA mitigated renal oxidative stress and suppressed the activation of TLR4/NF-kB pathway and the contents of downstream inflammatory response-related markers in the kidney. Moreover, FA remodeled the composition of gut microbiota, characterized by an increment in beneficial bacteria (e.g., Lactobacillus and Ruminococcus) and a decrement in pathogenic bacteria (e.g., Bacteroides). In conclusion, our study validated FA as an effective nutrition to ameliorate HFFD-induced HUA and implied the potential to mitigate its associated renal impairment and intestinal microbiota disturbance.