Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia

Abstract

Mangiferin, a natural glucosyl xanthone from the leaves of Mangifera indica L., was previously shown to exert potent hypouricemic effects associated with inhibition of the activity of xanthine dehydrogenase/ oxidase. The present study aimed to evaluate its uricosuric effect and possible molecular mechanisms underlying the renal urate transporters responsible for urate reabsorption in vivo. Mangiferin (1.5-24.0 mg/kg) was administered intragastrically to hyperuricemic mice and rats induced by the intraperitoneal injection of uric acid and potassium oxonate, respectively. The uricosuric effect was evaluated by determining the serum and urinary urate levels as well as fractional excretion of uric acid (FEUA). The mRNA and protein levels of renal urate-anion transporter 1 (URAT1), organic anion transporter 10 (OAT10), glucose transporter 9 (GLUT9), and PDZ domain-containing protein (PDZK1) were analyzed. The administration of mangiferin significantly decreased the serum urate levels in hyperuricemic mice in a dose-and time-dependent manner. In hyperuricemic rats, mangiferin also reduced the serum urate levels and increased the urinary urate levels and FEUA. These results indicate that mangiferin has uricosuric effects. Further examination showed that mangiferin markedly inhibited the mRNA and protein expression of renal URAT1, OAT10, and GLUT9 in hyperuricemic rats, but did not interfere with PDZK1 expression. Taken together, these findings suggest that mangiferin promotes urate excretion by the kidney, which may be related to the inhibition of urate reabsorption via downregulation of renal urate transporters.

Synergistic Uric Acid‐Lowering Effects of the Combination of Chrysanthemum indicum Linne Flower and Cinnamomum cassia (L.) J. Persl Bark Extracts

“…Therefore, increased FEUA can be interpreted as the increased excretion of renal uric acid. In the present study, uric acid levels in urine and FEUA reduced in the PO group compared to the NC group although there are reports demonstrating the uricosuric effect of PO [33, 34]. This observation is in agreement with finding of various reports [33, 34].…”

“…In the present study, uric acid levels in urine and FEUA reduced in the PO group compared to the NC group although there are reports demonstrating the uricosuric effect of PO [33, 34]. This observation is in agreement with finding of various reports [33, 34]. This discrepancy might be associated with the differences in approaches for administration periods and collecting time of urine.…”

Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling

“…We found that MG attenuated proteinuria and renal pathological damage, including deposition of IgG and C3, and improved renal function as well. The beneficial effects of MG on renal function have also been reported in multiple kidney injury models, such as chronic nephritis, acute renal injury [22,23], experimental hyperuricemia [24] and diabetic nephropathy [25,26], indicating that MG preserves renal function through a variety of mechanisms. Since many autoimmune diseases, including LN, are accompanied with a significant increase in serum autoantibodies, we determined whether MG would regulate autoantibody responses in B6/gld mice.…”

Mangiferin: A xanthonoid with multipotent anti‐inflammatory potential

“…However, attenuating the production of IL‐6, it potentially blocks the phosphorylation of JNK and p38, downstream of these signaling molecules, different apoptosis regulatory signals are activated . In another study with experimental model of hyperuricemia, mangiferin is shown to modulate the activity of the urate transporter and blocks the reabsorption of urate in the renal tissue , facilitating the excretion of uric acid. Different clinical studies suggest that acute renal injury is a common complication arising during the treatment of sepsis .…”