Clin Nutr Res.  2018 Apr;7(2):126-135. 10.7762/cnr.2018.7.2.126.

Hypouricemic Effect of Ethanol Extract of Aster glehni Leaves in Potassium Oxonate-Induced Hyperuricemic Rats

• Park JE
• Yeom Z
• Park KT
• Han EH
• Yu HJ
• Kang HS
• Lim YH

• KMID: 2409991
• DOI: http://doi.org/10.7762/cnr.2018.7.2.126

Abstract

The prevalence of gout is increasing worldwide, and control of serum uric acid level has been regarded as one of the therapeutic methods for gout. Inhibition of xanthine oxidase (XO) activity which can oxidize hypoxanthine to uric acid has been commonly proposed to decrease serum uric acid level. The aim of this study was to demonstrate the hypouricemic effect of ethanol extract of Aster glehni leaves (EAG) by in vitro and in vivo study in potassium oxonate (PO)-induced hyperuricemic rats. EAG possessed 132.5 ± 6.8 mg QE/g of total flavonoid and showed antioxidant activity. EAG showed in vitro and in vivo inhibitory activity against XO and significantly decreased serum uric acid level in PO-induced hyperuricemic rats without liver toxicity. These results show that EAG significantly attenuates hyperuricemia by inhibiting XO activity, which resulted in the decrease of serum uric acid level. Therefore, EAG might possess a potential therapeutic ability for improving gout.

Keyword

Aster glehni; Hyperuricemia; Xanthine oxidase; Serum uric acid

MeSH Terms

Animals
Ethanol*
Gout
Hyperuricemia
Hypoxanthine
In Vitro Techniques
Liver
Potassium*
Prevalence
Rats*
Uric Acid
Xanthine Oxidase
Ethanol
Hypoxanthine
Potassium
Uric Acid
Xanthine Oxidase

Figure

• 

  Figure 1 Effect of EAG on liver histology in PO-induced hyperuricemic rats. (A) Normal group, (B) hyperuricemia group induced by PO (250 mg/kg b.w.), (C) allopurinol (50 mg/kg b.w.) + PO, (D) EAG (50 mg/kg b.w.) + PO, (E) EAG (100 mg/kg b.w.) + PO, (F) EAG (200 mg/kg b.w.) + PO. All images were captured at 100× magnification.EAG, ethanol extract of Aster glehni leaves; PO, potassium oxonate.

• 

  Figure 2 Effect of EAG on serum uric acid levels in PO-induced hyperuricemic rats. Data represent mean ± standard deviation of 3 independent experiments performed in triplicate.EAG, ethanol extract of Aster glehni leaves; PO, potassium oxonate.*,†,‡,§Values not sharing a common superscript vary significantly (p < 0.05) from each other.

Reference

1. Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol. 2013; 9:13–23. PMID: 22945591.

2. Huang J, Wang S, Zhu M, Chen J, Zhu X. Effects of genistein, apigenin, quercetin, rutin and astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice. Food Chem Toxicol. 2011; 49:1943–1947. PMID: 21600261.

3. Perez-Ruiz F, Liote F. Lowering serum uric acid levels: what is the optimal target for improving clinical outcomes in gout? Arthritis Rheum. 2007; 57:1324–1328. PMID: 17907217.

4. Lin KC, Lin HY, Chou P. The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study. J Rheumatol. 2000; 27:1501–1505. PMID: 10852278.

5. Fels E, Sundy JS. Refractory gout: what is it and what to do about it? Curr Opin Rheumatol. 2008; 20:198–202. PMID: 18349751.

6. Li H, Zhao M, Su G, Lin L, Wang Y. Effect of soy sauce on serum uric acid levels in hyperuricemic rats and identification of flazin as a potent xanthine oxidase inhibitor. J Agric Food Chem. 2016; 64:4725–4734. PMID: 27181598.

7. Murugaiyah V, Chan KL. Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. J Ethnopharmacol. 2009; 124:233–239. PMID: 19397979.

8. Wang WL, Sheu SY, Huang WD, Chuang YL, Tseng HC, Hwang TS, Fu YT, Kuo YH, Yao CH, Kuo TF. Phytochemicals from tradescantia albiflora kunth extracts reduce serum uric acid levels in oxonate-induced rats. Pharmacogn Mag. 2016; 12:S223–S227. PMID: 27279711.

9. Wang M, Zhao J, Zhang N, Chen J. Astilbin improves potassium oxonate-induced hyperuricemia and kidney injury through regulating oxidative stress and inflammation response in mice. Biomed Pharmacother. 2016; 83:975–988. PMID: 27522260.

10. Lee HM, Yang G, Ahn TG, Kim MD, Nugroho A, Park HJ, Lee KT, Park W, An HJ. Antiadipogenic effects of Aster glehni extract: in vivo and in vitro effects. Evid Based Complement Alternat Med. 2013; 2013:859624. PMID: 23864899.

11. Samatha T, Shyamsundarachary R, Srinivas P, Swamy NR. Quantification of total phenolic and total flavonoid contents in extracts of Oroxylum indicum L.Kurz . Asian J Pharm Clin Res. 2012; 5:177–179.

12. Pontis JA, Costa LA, Silva SJ, Flach A. Color, phenolic and flavonoid content, and antioxidant activity of honey from Roraima, Brazil. Food Sci Technol (Campinas). 2014; 34:69–73.

13. Liu LM, Cheng SF, Shieh PC, Lee JC, Chen JJ, Ho CT, Kuo SC, Kuo DH, Huang LJ, Way TD. The methanol extract of Euonymus laxiflorus, Rubia lanceolata and Gardenia jasminoides inhibits xanthine oxidase and reduce serum uric acid level in rats. Food Chem Toxicol. 2014; 70:179–184. PMID: 24845958.

14. Azmi SM, Jamal P, Amid A. Xanthine oxidase inhibitory activity from potential Malaysian medicinal plant as remedies for gout. Int Food Res J. 2012; 19:59–66.

15. Liu K, Wang W, Guo BH, Gao H, Liu Y, Liu XH, Yao HL, Cheng K. Chemical evidence for potent xanthine oxidase inhibitory activity of ethyl acetate extract of Citrus aurantium L. dried immature fruits. Molecules. 2016; 21:302. PMID: 26950105.

16. Jang IT, Hyun SH, Shin JW, Lee YH, Ji JH, Lee JS. Characterization of an anti-gout xanthine oxidase inhibitor from Pleurotus ostreatus. Mycobiology. 2014; 42:296–300. PMID: 25346610.

17. Haidari F, Rashidi MR, Keshavarz SA, Mahboob SA, Eshraghian MR, Shahi MM. Effects of onion on serum uric acid levels and hepatic xanthine dehydrogenase/xanthine oxidase activities in hyperuricemic rats. Pak J Biol Sci. 2008; 11:1779–1784. PMID: 18817216.

18. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye-binding. Anal Biochem. 1976; 72:248–254. PMID: 942051.

19. Fukumoto LR, Mazza G. Assessing antioxidant and prooxidant activities of phenolic compounds. J Agric Food Chem. 2000; 48:3597–3604. PMID: 10956156.

20. Pietta PG. Flavonoids as antioxidants. J Nat Prod. 2000; 63:1035–1042. PMID: 10924197.

21. Calitz C, du Plessis L, Gouws C, Steyn D, Steenekamp J, Muller C, Hamman S. Herbal hepatotoxicity: current status, examples, and challenges. Expert Opin Drug Metab Toxicol. 2015; 11:1551–1565. PMID: 26149408.

22. Huang XJ, Choi YK, Im HS, Yarimaga O, Yoon E, Kim HS. Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors (Basel). 2006; 6:756–782.

23. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440:237–241. PMID: 16407889.

24. Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, Knott SA, Kolcic I, Polasek O, Graessler J, Wilson JF, Marinaki A, Riches PL, Shu X, Janicijevic B, Smolej-Narancic N, Gorgoni B, Morgan J, Campbell S, Biloglav Z, Barac-Lauc L, Pericic M, Klaric IM, Zgaga L, Skaric-Juric T, Wild SH, Richardson WA, Hohenstein P, Kimber CH, Tenesa A, Donnelly LA, Fairbanks LD, Aringer M, McKeigue PM, Ralston SH, Morris AD, Rudan P, Hastie ND, Campbell H, Wright AF. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet. 2008; 40:437–442. PMID: 18327257.

25. Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005; 353:2450–2461. PMID: 16339094.

26. Son MJ, Jin C, Lee YS, Lee JY, Kim HJ. Characterization of caffeoylglucoside derivatives and hypouricemic activity of the ethyl acetate fraction from Aster glehni . Bull Korean Chem Soc. 2015; 36:503–512.

27. Duni A, Liakopoulos V, Rapsomanikis KP, Dounousi E. Chronic kidney disease and disproportionally increased cardiovascular damage: does oxidative stress explain the burden. Oxid Med Cell Longev. 2017; 2017:9036450. PMID: 29333213.

28. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR; HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005; 293:1338–1347. PMID: 15769967.