Dietary Ferulic Acid Ameliorates Metabolism Syndrome-Associated Hyperuricemia in Rats via Regulating Uric Acid Synthesis, Glycolipid Metabolism, and Hepatic Injury

Abstract

Ferulic acid is a well-known phenolic acid compound and possesses multiple health-promoting and pharmacological effects. Metabolic syndrome (MetS) and hyperuricemia (HUA) have become health problems worldwide and are closely connected. The aim of this study was to explore the influence of ferulic acid on MetS-related HUA and its underlying mechanisms. Rats were administered high-fructose and high-fat diet (HFFD) with or without ferulic acid (0.05 and 0.1%) for 20 weeks. Intake of HFFD resulted in obesity, hyperglycemia, insulin resistance, and dyslipidemia, which were alleviated by ferulic acid consumption. Treatment of rats with ferulic acid diminished the levels of lipids and inflammatory cytokines and enhanced the activities of antioxidant enzymes in the liver caused by HFFD. Additionally, administration of ferulic acid blocked a HFFD-induced elevation in activities and mRNA expression of enzymes involving in uric acid (UA) synthesis. Molecular docking analysis denoted that ferulic acid bound to the active center of these enzymes, indicative of the potential interaction with each other. These two aspects might partially be responsible for the decrement in serum UA content after ferulic acid ingestion. In conclusion, ferulic acid supplementation ameliorated lipid and glucose metabolic abnormalities, hepatic damage, and UA formation in MetS rats. There was a dose correlation between lipid deposition and UA synthesis-related indicators. These findings implied that ferulic acid could be applied as a promising dietary remedy for the management of MetS-associated HUA.

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

“…Numerous studies demonstrated that natural components exert a positive effect on the management of these metabolic diseases owing to their wide range of biological activities, including FA as a familiar phenolic acid. 7,12,27 A previous study demonstrated that FA could not only alleviate HFFD-induced MetS, but could also suppress UA synthesis by weakening the activities and mRNA expression levels of associated enzymes, thereby exhibiting anti-hyperuricemic capacity in rats. 12 UA excretion in the kidneys and intestine, along with the gut microbiota are also critical to UA metabolism.…”

“…7,12,27 A previous study demonstrated that FA could not only alleviate HFFD-induced MetS, but could also suppress UA synthesis by weakening the activities and mRNA expression levels of associated enzymes, thereby exhibiting anti-hyperuricemic capacity in rats. 12 UA excretion in the kidneys and intestine, along with the gut microbiota are also critical to UA metabolism. However, the regulation of FA in these processes and related diseases is less clear.…”

“…The specific compositions of diets in different groups and the dosages of allopurinol and FA were determined based on a previous study (ESI Table S1 †). 12 The total duration of the experiment was 20 weeks.…”

“…[22][23][24] Previous investigations have also suggested that FA exhibits anti-hyperuricemic effects and could alleviate renal autophagy in diabetic mice. 12,25 The reduced serum UA level induced by FA in rats fed a HFFD could be partly due to the impact of FA on the activities and mRNA levels of UA synthesis-related enzymes in the liver. 12 Moreover, FA was reported to regulate the gut microbiota composition by elevating the relative abundance of beneficial bacteria and/or lowering that of harmful bacteria in mouse models of non-alcoholic fatty liver disease and atherosclerosis.…”

“…12,25 The reduced serum UA level induced by FA in rats fed a HFFD could be partly due to the impact of FA on the activities and mRNA levels of UA synthesis-related enzymes in the liver. 12 Moreover, FA was reported to regulate the gut microbiota composition by elevating the relative abundance of beneficial bacteria and/or lowering that of harmful bacteria in mouse models of non-alcoholic fatty liver disease and atherosclerosis. 26,27 Nevertheless, the specific anti-hyperuricemic mechanisms of FA remain unclear, and its modulation of HUA-associated renal damage and gut microbiota disorder in the condition of HFFD consumption remains to be clarified.…”