Melinjo seed extract stimulates intestinal ABCG2 expression to reduce serum uric acid levels in hyperuricemic rats

Abstract

• We examined the association between ABCG2 and MjR in hyperuricemia rats. • ABCG2 upregulation by MjR may play an important role in decreasing serum uric acid. • Gnemonoside D was likely the main component that increases ABCG2 expression. • MjR could have potential in the treatment of hyperuricemia. Melinjo resveratrol (MjR) is a resveratrol derivative from the seed extract of melinjo ( Gnetum gnemon L.). Although it may reduce serum uric acid concentration in humans, the underlying mechanism remains unclear. Thus, we investigated the effect of MjR on the uric acid metabolism in the setting of hyperuricemia model rats induced by orally administered oxonic acid. MjR administered for three weeks significantly lowered serum uric acid levels in hyperuricemia rats. While urinary excretion of uric acid did not change, fecal excretion of uric acid significantly increased by MjR. The expression of ATP-binding cassette sub-family G member (ABCG2) was upregulated with MjR treatment in the ileum but not in the kidney. In a human epithelial colorectal cell line, Caco-2, uric acid and MjR additively stimulated ABCG2 expression. These data suggest that MjR could reduce serum uric acid by enhancing fecal excretion of uric acid in the ileum by upregulating ABCG2 protein expression.