Seminar on Department of Food Science and Biotechnology of National Chung Hsing University
Title: Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine
oxidase activities in normal and hyperuricemic mice.
Speaker:孫楠辳
Moderator: 陳姵均
Student ID: 7101043035
Advisor: Chi-Fai Chau, Ph. D.
Date and Time: 2013/11/22 (NO. 1)
1. Introduction
Hyperuricemia is a key risk factor for the development of gout, and has been linked to renal
dysfunction, cardiovascular diseases, hypertension, hyperlipidemia, cancer, diabetes and metabolic
syndrome. Hyperuricemia occurs as a result of increased uric acid production, impaired renal uric acid
excretion, or a combination of these two conditions. Xanthine oxidase (XO) catalyses the oxidation of
hypoxanthine and xanthine to uric acid. Therefore, XO inhibitors have been proposed as potential
therapeutic agents for treating hyperuricemia as they could be used to block the biosynthesis of uric acid.
Allopurinol is the most commonly used xanthine oxidase inhibitor prescribed clinically for the treatment
of gout. However, its use is sometimes limited by hypersensitivity problems, Stevens –Johnson
syndrome, renal toxicity and even fatal liver necrosis.
It has been shown that some flavonoids in medicinal plants can change XO activities and serum uric
acid levels in vitro and in vivo. The aim of the present study was to determine the effects of the
flavonoids Genistein, Apigenin, Quercetin, Rutin and Astilbin on XO activities in vitro and in serum and
liver in vivo, as well as on serum uric acid levels in normal and potassium oxonate-induced
hyperuricemic mice. In addition, the renal function of the mice after flavonoid administration was
estimated by blood urea nitrogen (BUN) and creatinine analysis.
2. Materials and Methods
In vitro
Genistein
Apigenin
Quercetin
Rutin
Astilbin
Allopurinol
Xanthine oxidase
inhibitory activity
Hypouricemic effects in
normal and
hyperuricemic mice
In vivo
Serum and liver XO
activities in normal and
hyperuricemic mice
Effects on renal
functions
3. Results and Discussions
3.1. Xanthine oxidase inhibitory activity in vitro
Allopurinol inhibited XO activity in vitro. Genistein, Apigenin, Quercetin, Rutin and Astilbin
1
exhibited minimal or no XO inhibitory activity in vitro.
3.2. Hypouricemic effects of flavonoids in hyperuricemic mice
Serum uric acid levels of the hyperuricemic group treated with Allopurinol (10 mg/kg) for 7 days
was lowered significantly by 45.7%. The serum uric acid levels of hyperuricemic mice treated with
Quercetin (200 mg/kg), Rutin (75, 300 mg/kg) and Astilbin (1.0, 3.0 mg/kg) were lowered significantly
by 8.6–16.5%.
3.3. Hypouricemic effects of flavonoids in normal mice
Serum uric acid levels were not affected by Genistein (4.5, 9.0, 18.0 mg/kg) and Apigenin (175, 350,
700 mg/kg) However, serum uric acid levels in normal mice were significantly elevated by treatment
with Quercetin (100, 200, 400 mg/kg), Rutin (75, 150, 300 mg/kg) and Astilbin (1.0, 3.0, 9.0 mg/kg).
3.4. Serum and liver xanthine oxidase (XO) activities in hyperuricemic mice
Genistein (4.5 mg/kg) increased liver XO activity significantly but had no effect on serum XO
activity. Apigenin (700 mg/kg), Quercetin (100, 200 mg/kg), Rutin (150, 300 mg/kg) and Astilbin (1.0,
9.0 mg/kg) decreased liver XO activity significantly, but had no effect on serum XO activity. Moreover,
Genistein (9.0, 18.0 mg/kg), Apigenin (175, 350 mg/kg), Quercetin (400 mg/ kg), Rutin (75 mg/kg) and
Astilbin (3.0 mg/kg) had no effect on either serum or liver XO activities.
3.5. Serum and liver xanthine oxidase (XO) activities in normal mice
Genistein (4.5, 9.0, 18.0 mg/kg) and Apigenin (175, 350, 700 mg/kg) increased liver XO activities
significantly, but had no effect on serum XO activities. Quercetin (100, 200, 400 mg/kg), Rutin (75,
150, 300 mg/kg) and Astilbin (1.0, 3.0, 9.0 mg/kg) significantly increased serum XO activities. Except
for Rutin (150 mg/kg), all flavonoids decreased liver XO activities significantly.
3.6. Effects on renal functions
In hyperuricemic mice, Genistein (9.0 mg/kg), Rutin (150, 300 mg/kg) and Astilbin (1.0 mg/kg)
significantly decreased BUN levels. Apigenin (175, 350, 700 mg/kg) significantly increased BUN
levels. Genistein (18.0 mg/kg), Apigenin (175, 350, 700 mg/kg), Quercetin (100, 400 mg/kg) and Rutin
(75 mg/kg) significantly decreased creatinine levels.
In normal mice, Rutin (75, 150, 300 mg/kg), Astilbin (1.0, 9.0 mg/kg) significantly decreased BUN
levels compared with normal control mice not treated with flavonoids. Apigenin (175, 350 mg/kg)
significantly increased BUN levels. Genistein (18.0 mg/kg), Apigenin (700 mg/kg), Quercetin (100
mg/kg), Rutin (75, 150, 300 mg/kg) and Astilbin (3.0, 9.0 mg/kg) significantly decreased creatinine
levels.
4.Conclusion
All the flavonoids did not show any significant effect on XO activity in vitro, but did have a
significant effect on XO activities in vivo. Serum uric acid levels in mice treated with the flavonoids
tested here were higher than those in normal control mice. Therefore, the flavonoids tested here are not
candidates for replacing Allopurinol for the treatment of gout.
5.References
Huang J, Wang S, Zhu M, Chen JZ, Zhu XX. Effects of Genistein, Apigenin, Quercetin, Rutin
and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic
mice. Food and Chemical Toxicology. (2011) 49:1943-1947
2