Evaluating the Urate-lowering Effects of Different Microbial Fermented Extracts in Hyperuricemic Models Accompanied With a safety Study

Overview

Journal J Food Drug Anal

Specialties Nutritional Sciences
Pharmacology
Toxicology

Date 2017 Sep 16

PMID 28911646

Citations 12

Authors

Rong-Jane Chen

Mei-Huei Chen

Yen-Lin Chen

Ching-Mao Hsiao

Hsiu-Min Chen

Siao-Jhen Chen

Ming-Der Wu

Yi-Jen Yech

Gwo-Fang Yuan

Ying-Jan Wang

Affiliations

Soon will be listed here.

Abstract

Uric acid (UA) is an end product of purine metabolism by the enzyme xanthine oxidase (XOD). Hyperuricemia is characterized by the accumulation of serum UA and is an important risk factor for gout and many chronic disorders. XOD inhibitors or uricase (catalyzes UA to the more soluble end product) can prevent these chronic diseases. However, currently available hypouricemic agents induce severe side effects. Therefore, we developed new microbial fermented extracts (MFEs) with substantial XOD inhibition activity from Lactobacillus (MFE-21) and Acetobacter (MFE-25), and MFE-120 with high uricase activity from Aspergillus. The urate-lowering effects and safety of these MFEs were evaluated. Our results showed that MFE-25 exerts superior urate-lowering effects in the therapeutic model. In the preventive model, both MFE-120 and MFE-25 significantly reduced UA. The results of the safety study showed that no organ toxicity and no treatment-related adverse effects were observed in mice treated with high doses of MFEs. Taken together, the results showed the effectiveness of MFEs in reducing hyperuricemia without systemic toxicity in mice at high doses, suggesting that they are safe for use in the treatment and prevention of hyperuricemia.

Citing Articles

Study on the mechanism of lactic acid bacteria and their fermentation broth in alleviating hyperuricemia based on metabolomics and gut microbiota.

Rao L, Dong B, Chen Y, Liao J, Wang C, Fu G Front Nutr. 2024; 11:1495346.

PMID: 39698246 PMC: 11652139. DOI: 10.3389/fnut.2024.1495346.

06CC2 Enhanced the Expression of Intestinal Uric Acid Excretion Transporter in Mice.

Nei S, Matsusaki T, Kawakubo H, Ogawa K, Nishiyama K, Tsend-Ayush C Nutrients. 2024; 16(17).

PMID: 39275356 PMC: 11397172. DOI: 10.3390/nu16173042.

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential.

Li C, Wu C, Li F, Xu W, Zhang X, Huang Y J Inflamm Res. 2024; 17:1735-1763.

PMID: 38523684 PMC: 10960513. DOI: 10.2147/JIR.S460333.

The effects of free Cys residues on the structure, activity, and tetrameric stability of mammalian uricase.

Guo Y, Huo J, Bai R, Zhang J, Yao J, Ma K Appl Microbiol Biotechnol. 2023; 107(14):4533-4542.

PMID: 37256327 DOI: 10.1007/s00253-023-12597-y.

Alleviation of Hyperuricemia by Strictinin in AML12 Mouse Hepatocytes Treated with Xanthine and in Mice Treated with Potassium Oxonate.

Huang K, Chang Y, Pranata R, Cheng Y, Chen Y, Kuo P Biology (Basel). 2023; 12(2).

PMID: 36829604 PMC: 9953564. DOI: 10.3390/biology12020329.

References

Sampson L, Rimm E, Hollman P, de Vries J, Katan M . Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002; 102(10):1414-20. DOI: 10.1016/s0002-8223(02)90314-7. View

Zhou Y, Fang L, Jiang L, Wen P, Cao H, He W . Uric acid induces renal inflammation via activating tubular NF-κB signaling pathway. PLoS One. 2012; 7(6):e39738. PMC: 3382585. DOI: 10.1371/journal.pone.0039738. View

Juan M, Vinardell M, Planas J . The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. J Nutr. 2002; 132(2):257-60. DOI: 10.1093/jn/132.2.257. View

Gersch C, Palii S, Kim K, Angerhofer A, Johnson R, Henderson G . Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids. 2008; 27(8):967-78. PMC: 2701227. DOI: 10.1080/15257770802257952. View

Kimira M, Arai Y, Shimoi K, Watanabe S . Japanese intake of flavonoids and isoflavonoids from foods. J Epidemiol. 1998; 8(3):168-75. DOI: 10.2188/jea.8.168. View

Haidari F, Rashidi M, Keshavarz S, Mahboob S, Eshraghian M, Mohamad Shahi M . Effects of onion on serum uric acid levels and hepatic xanthine dehydrogenase/xanthine oxidase activities in hyperuricemic rats. Pak J Biol Sci. 2008; 11(14):1779-84. DOI: 10.3923/pjbs.2008.1779.1784. View

Reinders M, Jansen T . New advances in the treatment of gout: review of pegloticase. Ther Clin Risk Manag. 2010; 6:543-50. PMC: 2988614. DOI: 10.2147/TCRM.S6043. View

Edwards N . The role of hyperuricemia and gout in kidney and cardiovascular disease. Cleve Clin J Med. 2008; 75 Suppl 5:S13-6. DOI: 10.3949/ccjm.75.suppl_5.s13. View

Tung Y, Hsu C, Chen C, Yang S, Huang C, Chang S . Phytochemicals from Acacia confusa heartwood extracts reduce serum uric acid levels in oxonate-induced mice: their potential use as xanthine oxidase inhibitors. J Agric Food Chem. 2010; 58(18):9936-41. DOI: 10.1021/jf102689k. View

10.

Kong L, Yang C, Ge F, Wang H, Guo Y . A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice. J Ethnopharmacol. 2004; 93(2-3):325-30. DOI: 10.1016/j.jep.2004.04.008. View

11.

Chen Z, Wang Z, He X, Guo X, Li W, Zhang B . Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene. Appl Microbiol Biotechnol. 2008; 79(4):545-54. DOI: 10.1007/s00253-008-1472-8. View

12.

Alam N, Yoon K, Lee K, Kim H, Shin P, Cheong J . Assessment of Antioxidant and Phenolic Compound Concentrations as well as Xanthine Oxidase and Tyrosinase Inhibitory Properties of Different Extracts of Pleurotus citrinopileatus Fruiting Bodies. Mycobiology. 2012; 39(1):12-9. PMC: 3385085. DOI: 10.4489/MYCO.2011.39.1.012. View

13.

Feng J, Li X, Yang X, Zhang C, Yuan Y, Pu J . A new practical system for evaluating the pharmacological properties of uricase as a potential drug for hyperuricemia. Arch Pharm Res. 2010; 33(11):1761-9. DOI: 10.1007/s12272-010-1108-2. View

14.

Yu Z, Fong W, Cheng C . The dual actions of morin (3,5,7,2',4'-pentahydroxyflavone) as a hypouricemic agent: uricosuric effect and xanthine oxidase inhibitory activity. J Pharmacol Exp Ther. 2005; 316(1):169-75. DOI: 10.1124/jpet.105.092684. View

15.

Li J, Zhang X, Wang X, Xie Y, Kong L . Protective effects of cortex fraxini coumarines against oxonate-induced hyperuricemia and renal dysfunction in mice. Eur J Pharmacol. 2011; 666(1-3):196-204. DOI: 10.1016/j.ejphar.2011.05.021. View

16.

Yang X, Yuan Y, Zhan C, Liao F . Uricases as therapeutic agents to treat refractory gout: Current states and future directions. Drug Dev Res. 2012; 73(2):66-72. PMC: 3365602. DOI: 10.1002/ddr.20493. View

17.

Puddu P, Puddu G, Cravero E, Vizioli L, Muscari A . Relationships among hyperuricemia, endothelial dysfunction and cardiovascular disease: molecular mechanisms and clinical implications. J Cardiol. 2012; 59(3):235-42. DOI: 10.1016/j.jjcc.2012.01.013. View

18.

Jalal D, Chonchol M, Chen W, Targher G . Uric acid as a target of therapy in CKD. Am J Kidney Dis. 2012; 61(1):134-46. PMC: 3525781. DOI: 10.1053/j.ajkd.2012.07.021. View

19.

Niu Y, Zhu H, Liu J, Fan H, Sun L, Lu W . 3,5,2',4'-Tetrahydroxychalcone, a new non-purine xanthine oxidase inhibitor. Chem Biol Interact. 2010; 189(3):161-6. DOI: 10.1016/j.cbi.2010.12.004. View

20.

Hua J, Huang P, Zhu C, Yuan X, Yu C . Anti-hyperuricemic and nephroprotective effects of Modified Simiao Decoction in hyperuricemic mice. J Ethnopharmacol. 2012; 142(1):248-52. DOI: 10.1016/j.jep.2012.04.052. View