Urolithin C Ameliorates Hyperuricemia by Mitigating Renal Dysfunction through ROS-p38/ERK MAPK Axis Suppression

Area of Science:

• Metabolic disorders
• Gut microbiota
• Bioactive metabolites

Background:

• Hyperuricemia (HUA) is a common metabolic disorder with few treatment options.
• Urolithin C (UroC) is a metabolite derived from gut microbiota acting on ellagitannin-rich foods.

Purpose of the Study:

• To investigate the effects and mechanisms of UroC in managing HUA.
• To compare UroC with its analogs UroA and UroB in HUA treatment.

Main Methods:

• UFLC-MS/MS analysis to identify the active form of UroC in vivo.
• In vivo studies using HUA mice to assess UroC's impact on serum uric acid (SUA) levels.
• Mechanistic studies involving oxidative stress, fibrosis markers, and the ROS-p38/ERK MAPK signaling pathway.

Main Results:

• UroC significantly reduced SUA levels in HUA mice, outperforming UroA and UroB.
• Free UroC was identified as the primary active form in vivo.
• UroC enhanced renal uric acid excretion, reduced renal oxidative stress and fibrosis.
• UroC inhibited UA-induced p38/ERK MAPK activation by decreasing ROS production.
• Rescue experiments confirmed UroC's mechanism involving UA transporters and fibrosis markers via p38/ERK MAPK inhibition.

Conclusions:

• Urolithin C is a potent food-derived metabolite for managing hyperuricemia.
• UroC promotes renal protection and enhances uric acid excretion through the ROS-p38/ERK MAPK pathway.
• UroC represents a promising therapeutic candidate for hyperuricemia management.