INHIBITORY EFFECTS OF ANCHUSA AZUREA EXTRACTS ON XANTHINE OXIDASE ACTIVITY AND ITS HYPOURICEMIC EFFECTS ON MICE

Authors

  • Boussoualim N Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University Ferhat Abbas Setif 1, Setif 19000, Algeria
  • Baghiani A Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University Ferhat Abbas Setif 1, Setif 19000, Algeria
  • Krache I Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University Ferhat Abbas Setif 1, Setif 19000, Algeria
  • Trabsa H Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University Ferhat Abbas Setif 1, Setif 19000, Algeria
  • Kenouf S Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University Ferhat Abbas Setif 1, Setif 19000, Algeria
  • Arrar L. Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University Ferhat Abbas Setif 1, Setif 19000, Algeria

Keywords:

Anchusa azurea, Polyphenols, Flavonoids, Hyperuricemia, XO

Abstract

Objective: The aim of the present study was to determine the effects of the polyphenols and flavonoids from Anchusa azurea on XO activities in vitro and on serum and liver uric acid levels in normal and potassium oxonate-induced hyper uricemic mice. In addition, the renal function of the mice after flavonoid administration was estimated by the determination of blood urea and creatinine analysis.

Methods: In the present study, Anchusa azurea were extracted with solvent of varying polarity allowed its separation into four subfractions: crude extract (Cr) chloroform extract (ChE), ethyl acetate extract (AcE), and aqueous extracts (AqE). Total polyphenol and flavonoids contents of Anchusa azurea extracts were determined. The inhibitory activity of the extracts on the XO was evaluated and the type of inhibition was determined. Hyperuricemia is induced by intraperitoneally injection of potassium oxonate, the uric acid, urea and creatinine were measured in serum and supernatant of the liver. The effect of the extracts on renal function was evaluated. The rate of urea and creatinine levels can be indicators for the assessment of renal function.

Results: AcE were the richest in polyphenols and ChE was the richest fraction in flavonoids. The inhibitory activity of the extracts on the XO was evaluated, the results obtained showed that the inhibition is dose-dependent and ChE and AcE have the best inhibitory effect (IC50= 0.334±0.006 and 0.263±0.002 mg/ml, respectively), and both showed a noncompetitive type of inhibition. For antihyperuricemic effect, AqE and CrE caused a decrease in serum uric acid (a decrease of 66%) followed by ChE with a percentage of 29.22 %. The AcE keeps almost the same value of uric acid of "PO" group. For the supernatant, only CrE caused a significant decrease of liver uric acid (18.5±4.83 mg/l). This decrease can be explained by the significant inhibition of the XO by inhibition of the synthesis pathways of uric acid. Comparing the urea level of "OP" group (0.48 g/l), only extracts CrE-AA, AqE-AA (0.41g/l, 0.39 g/l) decreased the level of urea significantly (P ≤ 0.05) to the normal values of urea (0.34 g/l), we can conclude that the rate of urea and creatinine after treatment with plant extracts are normal and that the results of this study indicate the absence of renal damage in mice

Conclusion: Anchusa azurea fractions have a strong inhibitory effect on xanthine oxidase and also have a significant lowering effect on serum and liver creatinine and urea levels in hyper uricemic mice.

 

Downloads

Download data is not yet available.

References

Sachs L, Batra KL, Zimmermann B. Medical implications of hyperuricemia. Med Health 2009;92:353-5.

Unno T, Sugimoto A, Kakuda T. Xanthine oxidase inhibitors from the leaves of Lagerstroemia speciosa (L). Pers J Ethnopharmacol 2004;93:391-5.

Newcombe DS. Clinical aspects of gout and associated disease states. Chapter 5. In: Gout: Basic Science and Clinical Practice. London. Springer-Verlag; 2013. p. 91-159.

Hille R. Epr studies of xanthine oxidoreductase and othermolybdenum-containing hydroxylases. In: Metals in biology: Applications of High-Resolution EPR. London. Springer Science and Business Media; 2010. p. 92-120.

Chen P, Hung SI, Chen SY, Chen YT. Allopurinol. Chapter 13. In: Pharmacogenomic testing in current clinical practice, Molecular and translational medicine. London. Springer Science+Business Media; 2011. p. 213-22.

Bomalaski JS, Clark MA. Serum uric acid-lowering therapies: where are we heading in management of hyperuricemia and the potential role of uricase. Curr Rheumatoolgyl Rep 2004;6:240-7.

Yu Z, Fong WP, Cheng HK. 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 2006;316(1):169-75.

Lin CM, Chen CS, Chen CT, Liang YC, Lin JK. Molecular modeling of flavonoids that inhibits xanthine oxidase. Biochem Biophys Res Commun 2002;294:167-72.

Markham KR. Techniques of flavonoid identification. Academic press: London; 1982. p. 1-113.

Bahorun T, Gressier B, Trotin F, Brunete C, Dine T, Vasseur J, et al. Oxigen species scavenging activity of phenolic extract from howthorn fresh plant organs and pharmaceutical preparation. Arzneim Forsch/Drug Res 1996;46(11):1086-9.

Li HB, Cheng KW, Wong CC, Fan KW, Chen F, Jiang Y. Evaluation of antioxidant capacity and total phenolic content of different fractions of selected microalgae. Food Chem 2007;102:771-6.

Boumerfeg S, Baghiani A, Messaoudi D, Khennouf S, Arrar L. Antioxidant Properties and xanthine oxidase inhibitory effects of tamus communis L. Root Extracts. Phytother Res 2009;23:283-8.

Osada Y, Tsuchimoto M, Fukushima H, Takahashi K, Kondo S, Hasegawa M, et al. Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents. Eur J Pharmacol 1993;241:183-8.

Shi-Fu M, Feng Z, Yao-Zhong LV, Qing-Hua H, Dong-Mei Z, Ling-Dong K. Hypouricemic action of selected flavonoids in mice: structure-activity relationships. Biol Pharmacol Bull 2007;30(8):1551-6.

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;49:1943-7.

Cos P, Ying L, Calomme M, Hu JP, Cimanga K, Van Poel B, et al. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod 1998;61:71-6.

Arai T, Endo N, Yamashita K, Sasada M, Mori H, Ishii H, et al. 6-Formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation. Free Radical Biol Med 2001;3(1 Suppl 30):248-59.

Van Hoorn DEC, Nijveldt RJ, Van Leeuwen PAM, Hofman Z, M'Rabet L, De Bont DBA, et al. Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids. Eur J Pharmacol 2002;451:111-8.

Wu N, Zu Y, Fu Y, Kong Y, Zhao J, Li X, Li J, et al. Antioxidant activities and xanthine oxidase inhibitory effects of extracts and main polyphenolic compounds obtained from Geranium sibiricum L. J Agric Food Chem 2010;58:4737-43.

Tung YT, Chang ST. Inhibition of xanthine oxidase by Acacia confusa extracts and their phytochemicals. J Agric Food Chem 2010;58:781-6.

Baghiani A, Boumerfeg S, Belkhiri F, Khennouf S, Charef N, Harzallah D, et al. Antioxidant and radical scavenging properties of Carthamus caeruleus L. extracts grow wild in the Algeria flora. Comun Sci 2010;1:128-36.

Widyarini KD, Sukandar EY, Fidrianny I. Xanthine oxidase inhibitory and antihyperuricemic activities of anredera cordifolia (ten) Steenis, Sonchus Arvensis L. and its combination. Int J Pharm Pharm Sci 2015;7(3):87-90.

Aucamp J, Gaspar A, Hara Y, Apostolides Z. Inhibition of xanthine oxidase by catechins from tea (Camellia sinensis). Anticancer Res 1997;17:4381-5.

Berboucha M, Ayouni K, Atmani D, Atmani Dj, Benboubetra M. Kinetic study on the inhibition of xanthine oxidase by extracts from two selected algerian plants traditionally used for the treatment of inflammatory diseases. J Med Food 2010;13(4):1-9.

Zhu JX, Wang Y, Kong LD, Yang C, Zhang X. Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine aoxidase activities in mouse liver. J Ethnopharmacol 2004;93:133-40.

Published

01-08-2015

How to Cite

N, B., B. A, K. I, T. H, K. S, and A. L. “INHIBITORY EFFECTS OF ANCHUSA AZUREA EXTRACTS ON XANTHINE OXIDASE ACTIVITY AND ITS HYPOURICEMIC EFFECTS ON MICE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 8, Aug. 2015, pp. 195-9, https://journals.innovareacademics.in/index.php/ijpps/article/view/6845.

Issue

Section

Original Article(s)