Hypouricemic Effects of Chrysanthemum indicum L. and Cornus officinalis on Hyperuricemia-Induced HepG2 Cells, Renal Cells, and Mice.

Ok-Kyung Kim,Dakyung Kim,Jeongmin Lee,Jeong-Moon Yun,Minhee Lee

doi:10.3390/plants10081668

Abstract

Hyperuricemia, abnormally excess accumulation of uric acid, is caused by an imbalance between the production and excretion of uric acid and is a major cause of gout. We compared the effects of extracts from Chrysanthemum indicum L. (Ci) and Cornus officinalis Siebold and Zucc. (Co) on hyperuricemia, both individually and in combination (FSU-CC), using hypoxanthine-treated human liver cancer (HepG2) cells, primary mouse renal proximal tubule cells, and potassium oxonate induced hyperuricemic mice. The Ci contained 7.62 mg/g luteolin and 0 mg/g loganin, Co contained 0 mg/g luteolin and 4.90 mg/g loganin, and FSH-CC contained 3.95 mg/g luteolin and 2.48 mg/g loganin. We found that treatment with Ci, Co, and FSU-CC suppressed the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase while inducing an increase in the expression levels of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) proteins and a decrease in the expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins. Particularly, treatment and supplementation with FSU-CC showed stronger effects than those of supplementation with either Ci or Co alone. We observed that the excretion of creatinine and uric acid in the combination of Ci and Co was higher than that observed in their individual supplementations and was similar to that of the normal group. Therefore, our data suggest that a combination of Ci and Co may potentially be used for the development of effective natural anti-hyperuricemic functional foods.

Highlights

Purines play important roles as the precursors of nucleic acids, DNA and RNA, promoting the growth, proliferation, and survival of all cells
Uric acid reabsorption occurs in the renal proximal tubules, facilitated by transporters such as glucose transporter 9 (GLUT9), urate anion transporter 1 (URAT1), and organic anion transporter 4 (OAT4), while uric acid excretion is facilitated by transporters such as organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3)
We found that hypoxanthine treatment (C) increased the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase as compared with those in the normal control (NC)

Summary

Introduction

Purines play important roles as the precursors of nucleic acids, DNA and RNA, promoting the growth, proliferation, and survival of all cells. Excess accumulation of uric acid, known as hyperuricemia, is caused by an imbalance between the production and excretion of uric acid [2]. Uric acid is produced by the activities of xanthine oxidase and xanthine dehydrogenase, together referred to as “xanthine oxidoreductase”, in the liver. Xanthine oxidoreductase catalyzes the oxidation of hypoxanthine to xanthine and later to uric acid [5,6]. During the production of uric acid, xanthine oxidase delivers electrons directly to molecular oxygen, generating the reactive oxygen species (ROS), including the superoxide anion (O2−) and hydrogen peroxide (H2O2), which can further induce oxidative stress [8]. Maintaining the function of these uric acid transporters is important to prevent hyperuricemia [10,11]

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