EFFECTS OF PHENOLIC COMPOUNDS EXTRACTED FROM SALVIA FRIGIDA ON INDUCED HYPERURICEMIA IN MICE

  • MUHAMMAD ABDULHUSSEIN AL-DABBAGH Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
  • SHIHAB ABDULRAHMAN SHIHAB Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
  • ENAS JAWAD KADHIM Department of Pharmacognosy, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

Abstract

Objective: The aim of this study was to investigate effects of phenolic compounds rich fraction extracted from aerial parts of Salvia frigida on serum uric acid (SUA) and xanthine oxidase (XOD) in hyperuricemic mice model.


Methods: A total of 40 albino male mice were equally divided into four groups. The blank group was given vehicles only. The model of hyperuricemia was induced by single intraperitoneal injection of UA (250 mg/kg). S. frigida group was pretreated orally with phenolic compounds rich fraction (300 mg/kg) for 6 days and one final oral dose was given directly after the UA injection on the 7th day as an acute treatment and the same was applied to allopurinol (20 mg/kg) which served as a positive control. 1 h later blood was withdrawn to be tested for SUA, XOD, and creatinine levels. Furthermore, the body weights were daily documented before each administration.


Results: The results revealed a highly comparable significant reduction in SUA and XOD in both S. frigida and allopurinol groups without significantly affecting serum creatinine compared to model group, also both modestly decreased the body weights of mice.


Conclusion: S. frigida significantly reduces SUA in the hyperuricemic model and may also have a promising effect on weight management.

Keywords: Uric acid, Xanthine oxidase, Urate lowering therapy, Flavonoids, Quercetin, Allopurinol.

Author Biographies

MUHAMMAD ABDULHUSSEIN AL-DABBAGH, Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.

B.Sc. Pharmacy (2011), M.Sc. Pharmacology (2019)

Pharmacology Department

SHIHAB ABDULRAHMAN SHIHAB, Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.

Lecturer

M.B.Ch.B., Ph.D. Pharmacology

Pharmacology Department

ENAS JAWAD KADHIM, Department of Pharmacognosy, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

Assistant Professor

B.Sc. Pharmacy, M.Sc. & Ph.D. Pharmacognosy

Head of Pharmacognosy Department

References

1. Song P, Wang H, Xia W, Chang X, Wang M, An L, et al. Prevalence and correlates of hyperuricemia in the middle-aged and older adults in China. Sci Rep 2018;8:4314.
2. El-Yassin HD, Al-Sharifi ZA, Al-Jebuori S. Prevalence of hyperuricemia and its correlation with cardiovascular risk factors in Iraqi subjects of Karbalaa city. J Fac Med Baghdad 2012;54:83-7.
3. Preitner F, Bonny O, Laverrière A, Rotman S, Firsov D, Da Costa A, et al. Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy. Proc Natl Acad Sci U S A 2009;106:15501-6.
4. Brito R, Castillo G, González J, Valls N, Rodrigo R. Oxidative stress in hypertension: Mechanisms and therapeutic opportunities. Exp Clin Endocrinol Diabetes 2015;123:325-35.
5. Dhandapani C, Shibulal JS, Narayanasamy K. Metabolic evaluation of patients with recurrent and multiple renal stones: A prospective study. Asian J Pharm Clin Res 2016;9 Suppl 3:212-8.
6. Kanbay M, Jensen T, Solak Y, Le M, Roncal-Jimenez C, Rivard C, et al. Uric acid in metabolic syndrome: From an innocent bystander to a central player. Eur J Intern Med 2016;29:3-8.
7. Martinez-Quintana E, Tugores A, Rodriguez-Gonzalez F. Serum uric acid levels and cardiovascular disease: The Gordian knot. J Thorac Dis 2016;8:E1462-6.
8. Tripathi GK, Sharma R, Verma M, Sharma P, Kumar P. Biomarkers in serum, uric acid as a risk factor for Type 2 diabetes associated with hypertension. Asian J Pharm Clin Res 2016;9:352-5.
9. Wannamethee SG, Papacosta O, Lennon L, Whincup PH. Serum uric acid as a potential marker for heart failure risk in men on antihypertensive treatment: The British regional heart study. Int J Cardiol 2018;252:187 92.
10. Gliozzi M, Malara N, Muscoli S, Mollace V. The treatment of hyperuricemia. Int J Cardiol 2016;213:23-7.
11. Boussoualim N, Baghiani A, Krache I, Trabsa H, Kenouf S, Arrar L. Inhibitory effects of Anchusa azurea extracts on xanthine oxidase activity and its hypouricemic effects on mice. Int J Pharm Pharm Sci 2015;7:195-9.
12. Wahyuningsih S, Sukandar EY, Sukrasno, Lofika DN. Antihyperuricemia activity of the ethanol extract of roselle calyx and its fraction (Hibiscus sabdariffa Linn) on male wistar rats. Int J Pharm Pharm Sci 2016;8:278-80.
13. Orhan I, Kartal M, Naz Q, Ejaz A, Yilmaz G, Kan Y, et al. Antioxidant and anticholinesterase evaluation of selected Turkish Salvia species. Food Chem 2007;103:1247-54.
14. Kadhim EJ. Phytochemical Investigation and Testing the Effect of Iraqi Echinops heterophyllus Family Compositae on Wound Healing [Dissertation]. Baghdad: University of Baghdad; 2013.
15. Khadim EJ, Abdulrasool AA, Awad ZJ. Phytochemical investigation of alkaloids in the Iraqi Echinops heterophyllus (Compositae). Iraqi J Pharm Sci 2014;23:26-34.
16. Vimalkumar CS, Hosagaudar VB, Suja SR, Vilash V, Krishnakumar NM, Latha PG. Comparative preliminary phytochemical analysis of ethanolic extracts of leaves of Olea dioica Roxb., Infected with the rust fungus Zaghouania oleae (E.J. Butler) Cummins and non-infected plants. J Pharmacogn Phytochem 2014;3:69-72.
17. Hamad MN. Isolation of rutin from Ruta graveolens (Rutaceae) cultivated in Iraq by precipitation and fractional solubilization. Pharm Glob 2012;3:1-3.
18. Orhan IE, Tosun FA, Kök AF. Quantification of genistein and daidzein in two endemic Genista species and their antioxidant activity. J Serb Chem Soc 2011;76:35-42.
19. Chen GL, Wei W, Xu SY. Effect and mechanism of total saponin of dioscorea on animal experimental hyperuricemia. Am J Chin Med 2006;34:77-85.
20. Kamal SE, Zulfiah RA, Hasyim MF, Jayanti AD. The antipyretic effects test of ethanol extracts of green chiretta herbs (Andrographis paniculata Nees) on male mice (Musmusculus). Dama Int J Res 2017;2:9-15.
21. Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006;58:87-114.
22. Voskou S, Aslan M, Fanis P, Phylactides M, Kleanthous M. Oxidative stress in ?-thalassaemia and sickle cell disease. Redox Biol 2015;6:226 39.
23. Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant-and radical-caused aging and cancer: A hypothesis. Proc Natl Acad Sci U S A 1981;78:6858-62.
24. Neogi T, George J, Rekhraj S, Struthers AD, Choi H, Terkeltaub RA, et al. Are either or both hyperuricemia and xanthine oxidase directly toxic to the vasculature? A critical appraisal. Arthritis Rheum 2012;64:327 38.
25. Hayden MR, Tyagi SC. Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and Type 2 diabetes mellitus: The urate redox shuttle. Nutr Metab (Lond) 2004;1:10.
26. Battelli MG, Bortolotti M, Polito L, Bolognesi A. The role of xanthine oxidoreductase and uric acid in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis 2018;1864:2557-65.
27. Wang R, Ma CH, Zhou F, Kong LD. Siwu decoction attenuates oxonate-induced hyperuricemia and kidney inflammation in mice. Chin J Nat Med 2016;14:499-507.
28. Qin Z, Wang S, Lin Y, Zhao Y, Yang S, Song J, et al. Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice. Acta Pharm Sin B 2018;8:306-15.
29. Cao T, Li X, Mao T, Liu H, Zhao Q, Ding X, et al. Probiotic therapy alleviates hyperuricemia in C57BL/6 mouse model. Biomed Res 2017;28:2244-49.
30. Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF, et al. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: Structure-based mechanism of conversion. Proc Natl Acad Sci U S A 2000;97:10723-8.
31. Hayyan M, Hashim MA, AlNashef IM. Super oxide ion: Generation and chemical implications. Chem Rev 2016;116:3029-85.
32. Dawson J, Walters M. Uric acid and xanthine oxidase: Future therapeutic targets in the prevention of cardiovascular disease? Br J Clin Pharmacol 2006;62:633-44.
33. Godber BL, Doel JJ, Durgan J, Eisenthal R, Harrison R. A new route to peroxynitrite: A role for xanthine oxidoreductase. FEBS Lett 2000;475:93-6.
34. Babior BM. The leukocyte NADPH oxidase. Isr Med Assoc J 2002;4:1023-4.
35. Xu P, LaVallee P, Hoidal JR. Repressed expression of the human xanthine oxidoreductase gene. J Biol Chem 2000;275:5918-26.
36. Wu X, Wakamiya M, Vaishnav S, Geske R, Montgomery C Jr., Jones P, et al. Hyperuricemia and urate nephropathy in urate oxidase-deficient mice. Proc Natl Acad Sci U S A 1994;91:742-6.
37. Kadhum HH. Evaluation of Protective Effects of L-carnitine, Atorvastatin, and Vitamin A on Acetaminophen Induced Hepatotoxicity and Nephrotoxicity in Rats [Thesis]. Baghdad: Al-Nahrain University; 2015.
38. Jiang Y, Lin Y, Hu YJ, Song XJ, Pan HH, Zhang HJ, et al. Caffeoylquinic acid derivatives rich extract from Gnaphalium pensylvanicum willd. Ameliorates hyperuricemia and acute gouty arthritis in animal model. BMC Complement Altern Med 2017;17:320.
39. Mo SF, Zhou F, Lv YZ, Hu QH, Zhang DM, Kong LD. Hypouricemic action of selected flavonoids in mice: Structure–activity relationships. Biol Pharm Bull 2007;30:1551-6.
40. Hu QH, Wang C, Li JM, Zhang DM, Kong LD. Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: Renal organic ion transporter involvement. Am J Physiol Renal Physiol 2009;297:F1080-91.
41. West J. How Enzyme Activity Changes as Enzyme Concentration Decreases. Sciencing. Available from: https://www.sciencing.com/enzyme-activity-changes-enzyme-concentration-decreases-10250.html. [Last accessed on 2018 Mar 13].
42. McNally JS, Saxena A, Cai H, Dikalov S, Harrison DG. Regulation of xanthine oxidoreductase protein expression by hydrogen peroxide and calcium. Arterioscler Thromb Vasc Biol 2005;25:1623-8.
43. Azevedo MI, Pereira AF, Nogueira RB, Rolim FE, Brito GA, Wong DV, et al. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Mol Pain 2013;9:53.
44. Acharya CR, Sharma AK, Kanthari ND. Involvement of oxidative stress in patients of gout and antioxidant effect of allopurinol. Int J Med Sci Public Health 2015;4:168-72.
45. Cicerchi C, Li N, Kratzer J, Garcia G, Roncal-Jimenez CA, Tanabe K, et al. Uric acid-dependent inhibition of AMP kinase induces hepatic glucose production in diabetes and starvation: Evolutionary implications of the uricase loss in hominids. FASEB J 2014;28:3339 50.
46. Fujimura Y, Yamauchi Y, Murase T, Nakamura T, Fujita SI, Fujisaka T, et al. Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients. PLoS One 2017;12:e0182699.
47. Tsushima Y, Nishizawa H, Tochino Y, Nakatsuji H, Sekimoto R, Nagao H, et al. Uric acid secretion from adipose tissue and its increase in obesity. J Biol Chem 2013;288:27138-49.
48. Sodhi K, Hilgefort J, Banks G, Gilliam C, Stevens S, Ansinelli HA, et al. Uric acid-induced adipocyte dysfunction is attenuated by HO-1 upregulation: Potential role of antioxidant therapy to target obesity. Stem Cells Int 2016;2016:8197325.
49. Battelli MG, Polito L, Bolognesi A. Xanthine oxidoreductase in atherosclerosis pathogenesis: Not only oxidative stress. Atherosclerosis 2014;237:562-7.
50. Seo S, Lee MS, Chang E, Shin Y, Oh S, Kim IH, et al. Rutin increases muscle mitochondrial biogenesis with AMPK activation in high-fat diet-induced obese rats. Nutrients 2015;7:8152-69.
Statistics
112 Views | 75 Downloads
Citatons
How to Cite
MUHAMMAD ABDULHUSSEIN AL-DABBAGH, SHIHAB ABDULRAHMAN SHIHAB, and ENAS JAWAD KADHIM. “EFFECTS OF PHENOLIC COMPOUNDS EXTRACTED FROM SALVIA FRIGIDA ON INDUCED HYPERURICEMIA IN MICE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 4, Mar. 2019, pp. 211-7, doi:10.22159/ajpcr.2019.v12i4.32096.
Section
Original Article(s)