Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia

Abstract

BackgroundExcessive production and/or reduced excretion of uric acid could lead to hyperuricemia, which could be a major cause of disability. Hyperuricemia has received increasing attention in the last few decades due to its global prevalence. Cichorium intybus L., commonly known as chicory, is a perennial herb of the asteraceae family. It was previously shown to exert potent hypouricemic effects linked with decreasing uric acid formation in the liver by down-regulating the activity of xanthine oxidase, and increasing uric acid excretion by up-regulating the renal OAT3 mRNA expression. The present study aimed to evaluate its extra-renal excretion and possible molecular mechanism underlying the transporter responsible for intestinal uric acid excretion in vivo.MethodsChicory was administered intragastrically to hyperuricemic rats induced by drinking 10% fructose water. The uricosuric effect was evaluated by determining the serum uric acid level as well as the intestinal uric acid excretion by HPLC. The location and expression levels of ATP-binding cassette transporter, sub-family G, member 2 (ABCG2) in jejunum and ileum were analyzed.ResultsThe administration of chicory decreased the serum uric acid level significantly and increased the intestinal uric acid excretion obviously in hyperuricemic rats induced by 10% fructose drinking. Staining showed that ABCG2 was expressed in the apical membrane of the epithelium and glands of the jejunum and ileum in rats. Further examination showed that chicory enhanced the mRNA and protein expressions of ABCG2 markedly in a dose-dependent manner in jejunum and ileum.ConclusionThese findings indicate that chicory increases uric acid excretion by intestines, which may be related to the stimulation of intestinal uric acid excretion via down-regulating the mRNA and protein expressions of ABCG2.

Construction and expression of recombinant uricase‑expressing genetically engineered bacteria and its application in rat model of hyperuricemia

“…In the present study, the analysis of the whole contents of the small intestine, SUA values and allantoin values in rats suggested that uricase-expressing genetically engineered bacteria colonized the intestine and served a role in lowering uric acid levels. In addition, one study has used montmorillonite to adsorb intestinal uric acid in order to decrease SUA levels (55), which is consistent with the results of the present study. However, the aforementioned study only analyzed the effect of adsorption of intestinal uric acid by montmorillonite on SUA in a short period of time, but the effect of long-term use of montmorillonite on SUA was not analyzed.…”

Bioactive Compounds from Plant-Based Functional Foods: A Promising Choice for the Prevention and Management of Hyperuricemia

“…They confirmed that ABCG2 is involved in the intestinal excretion of UA in humans and rats as an extrarenal excretion pathway, thereby providing some clarification regarding UA metabolism along the intestine by focusing on a novel UA exporter, ABCG2 [126]. Furthermore, Wang et al [127] confirmed that chicory extract ameliorates intestinal UA elimination by modulating the ABCG2 transporter. In 10% fructose-induced HUA rats, the administration of chicory water extract (6.6 g/kg) significantly reduced SUA levels, and significantly increased intestinal UA excretion (p < 0.05).…”

Uricostatic and uricosuric effect of grapefruit juice in potassium oxonate‐induced hyperuricemic mice

“…Recently, we observed that stevia residue extract attenuate hyperuricemia via upregulating ABCG2 transporter in small intestinal tissues in hyperuricemic mice (Mehmood, Zhao, Wang, Hossen, Raka, et al, 2019). Similarly, Wang et al (2017) also observed the decrease in the intestinal ABCG2 expression (model group) in fructose‐induced hyperuricemic rat which was upregulated by the administration of chicory extract. Resveratrol was also reported to uricosuric effect in experimental hyperuricemic mice via upregulating the intestinal and renal ABCG2 expression (Wang et al, 2016).…”

“…The GFJ and allopurinol upregulated the ABCG2 expression in renal, small and large intestinal tissues which confirmed that GFJ contributes in the uric acid excretion (Figure 2c). Previously, many authors reported the modulatory effect of fruits and vegetables extract on the ABCG2 expression in various animal models (Chen et al, 2019; Mehmood, Zhao, Wang, Hossen, Raka, et al, 2019; Mehmood, Zhao, Wang, Nadeem, et al, 2019; Qian et al, 2019; Wang et al, 2017). Recently, we observed that stevia residue extract attenuate hyperuricemia via upregulating ABCG2 transporter in small intestinal tissues in hyperuricemic mice (Mehmood, Zhao, Wang, Hossen, Raka, et al, 2019).…”