Kinetics of Inhibition of Xanthine Oxidase by Globularia alypum and its Protective Effect against Oxonate-Induced Hyperuricemia and Renal Dysfunction in Mice.

ABSTRACT

In the present study, Globularia alypum (GA) was extracted with solvent of varying polarity allowed its separation into four subtractions crude extract (CrE) chloroform extract (ChE), ethyl acetate extract (AcE) and aqueous extracts (AqE). The results showed that AcE had the highest content of phenolic compounds. The inhibitory activity of the extracts on xanthine oxidase (XO) was evaluated, the results obtained showed that the inhibition is dose-dependent and the AcE had a very significant inhibitory effect (0.069 ± 0.003 mg/ml) followed by CrE and AqE (0.081 ± 0.000 et 0.088 ± 0.002 mg/ml, respectively). The CrE, ChE and AqE inhibit competitively XO, whereas AcE is a non-competitive inhibitor. Hyperuricemia was induced by intraperitoneally injection of potassium oxonate, the uric acid, urea and creatinine were measured in serum and liver supernatant. The ChE, AcE, and AqE extracts had reduced significantly the plasma and liver uric acid levels (decreased 44.76%, 43.03% and 31.31%, respectively). Comparing these results with those obtained in vitro, the ChE extract with the lowest inhibitory effect in vitro (IC50 = 0,123 mg / ml) was the most effective extract in vivo. In summary, there was a contradiction between inhibition in vitro and in vivo, this inconsistency or difference may be due to the difference in the bioavailability of flavonoids or natural substances and their extensive metabolism in mice.