Saengmaeksan, a Traditional Herbal Formulation Consisting of , Ameliorates Hyperuricemia by Inhibiting Xanthine Oxidase Activity and Enhancing Urate Excretion in Rats

Overview

Journal J Ginseng Res

Date 2021 Nov 22

PMID 34803426

Citations 7

Authors

Yoon-Young Sung

Heung Joo Yuk

Dong-Seon Kim

Affiliations

Soon will be listed here.

Abstract

Background: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, , , and . SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown.

Methods: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC).

Results: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1β levels in both the serum and kidneys. SMS-E inhibited both XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W.

Conclusion: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

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References

Lee Y, Chin Y, Choi Y . Effects of Korean red ginseng extract on acute renal failure induced by gentamicin and pharmacokinetic changes by metformin in rats. Food Chem Toxicol. 2013; 59:153-9. DOI: 10.1016/j.fct.2013.05.025. View

Zhang Y, Su H, Zhang J, Kong J . The Effects of Ginsenosides and Anserine on the Up-Regulation of Renal Aquaporins 1-4 in Hyperuricemic Mice. Am J Chin Med. 2019; 47(5):1133-1147. DOI: 10.1142/S0192415X19500587. View

Singh J, Reddy S, Kundukulam J . Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol. 2011; 23(2):192-202. PMC: 4104583. DOI: 10.1097/BOR.0b013e3283438e13. View

Tang D, Ye Y, Wang C, Li Z, Zheng H, Ma K . Potassium oxonate induces acute hyperuricemia in the tree shrew (tupaia belangeri chinensis). Exp Anim. 2017; 66(3):209-216. PMC: 5543241. DOI: 10.1538/expanim.16-0096. View

Strilchuk L, Fogacci F, Cicero A . Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin Drug Saf. 2019; 18(4):261-271. DOI: 10.1080/14740338.2019.1594771. View

Jeong M, Park D, Kim M, Park J, Kim D, Jeon Y . Saengmaeksan inhibits inflammatory mediators by suppressing RIP-2/caspase-1 activation. Immunopharmacol Immunotoxicol. 2013; 35(2):241-50. DOI: 10.3109/08923973.2012.757617. View

Attele A, Wu J, Yuan C . Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999; 58(11):1685-93. DOI: 10.1016/s0006-2952(99)00212-9. View

Lipkowitz M . Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep. 2012; 14(2):179-88. DOI: 10.1007/s11926-012-0240-z. View

Zhu P, Li J, Fu X, Yu Z . Schisandra fruits for the management of drug-induced liver injury in China: A review. Phytomedicine. 2019; 59:152760. DOI: 10.1016/j.phymed.2018.11.020. View

10.

Viazzi F, Leoncini G, Ratto E, Pontremoli R . Hyperuricemia and renal risk. High Blood Press Cardiovasc Prev. 2014; 21(3):189-94. DOI: 10.1007/s40292-014-0042-7. View

11.

Chohan S . Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions. J Rheumatol. 2011; 38(9):1957-9. DOI: 10.3899/jrheum.110092. View

12.

Wu A, Gladden J, Ahmed M, Ahmed A, Filippatos G . Relation of serum uric acid to cardiovascular disease. Int J Cardiol. 2015; 213:4-7. DOI: 10.1016/j.ijcard.2015.08.110. View

13.

Baek S, Shin B, Kim N, Chang S, Park J . Protective effect of ginsenosides Rk3 and Rh4 on cisplatin-induced acute kidney injury and . J Ginseng Res. 2017; 41(3):233-239. PMC: 5489750. DOI: 10.1016/j.jgr.2016.03.008. View

14.

Lee D, Lee J, Vu-Huynh K, Van Le T, Do T, Hwang G . Protective Effect of Panaxynol Isolated from against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies. Biomolecules. 2019; 9(12). PMC: 6995609. DOI: 10.3390/biom9120890. View

15.

Yousef M, Hussien H . Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng. Food Chem Toxicol. 2015; 78:17-25. DOI: 10.1016/j.fct.2015.01.014. View

16.

Kim M, Yoo Y, Sung N, Lee J, Park S, Shon E . Anti-Inflammatory Effects of Liriope platyphylla in LPS-Stimulated Macrophages and Endotoxemic Mice. Am J Chin Med. 2016; 44(6):1127-1143. DOI: 10.1142/S0192415X16500634. View

17.

Park K, Lee M, Kang H, Kim K, Lee S, Cho I . Saeng-Maek-San, a medicinal herb complex, protects liver cell damage induced by alcohol. Biol Pharm Bull. 2002; 25(11):1451-5. DOI: 10.1248/bpb.25.1451. View

18.

Matsuo H, Nakayama A, Sakiyama M, Chiba T, Shimizu S, Kawamura Y . ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload. Sci Rep. 2014; 4:3755. PMC: 3895923. DOI: 10.1038/srep03755. View

19.

Su J, Wei Y, Liu M, Liu T, Li J, Ji Y . Anti-hyperuricemic and nephroprotective effects of Rhizoma Dioscoreae septemlobae extracts and its main component dioscin via regulation of mOAT1, mURAT1 and mOCT2 in hypertensive mice. Arch Pharm Res. 2014; 37(10):1336-44. DOI: 10.1007/s12272-014-0413-6. View

20.

Bao R, Liu M, Wang D, Wen S, Yu H, Zhong Y . Effect of Stem Extract on Uric Acid Excretion in Hyperuricemia Mice. Front Pharmacol. 2020; 10:1464. PMC: 6914847. DOI: 10.3389/fphar.2019.01464. View