3,5-Dicaffeoylquinic acid promotes intestinal urate excretion via the MAPK signaling pathway based on Caco-2 Cell model

Hyperuricemia is a metabolic disease caused by excessive production of uric acid or abnormal excretion of uric acid. Although most of the uric acid is excreted in the kidneys, the elimination of uric acid in the intestines still plays an important role. 3,5-dicaffeoylquinic acid (3,5-diCQA) is widely found in Chrysanthemum and Artemisia species, where it inhibits the activity of xanthine oxidase (XOD), a key enzyme in uric acid production. Therefore, a Caco-2 cell model was utilized to explore the mechanisms of 3,5-diCQA affecting uric acid excretion under high uric acid conditions, focusing on aspects such as intestinal uric acid transport, the intestinal barrier, and the MAPK signaling pathway. The results showed that 3,5-diCQA could reduce the oxidative stress and apoptosis induced by high uric acid, repair the intestinal barrier, upregulate the expression of ABCG2 and MRP4, promote the excretion of uric acid and inhibit the activation of MAPK signaling pathway. In addition, 3,5-diCQA could also regulate the expression of ABCG2 and MRP4 via the MAPK signaling pathway. These findings provide scientific evidence for dietary recommendations for individuals with hyperuricemia, suggesting that foods or supplements containing 3,5-diCQA may help manage uric acid levels.