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Background  Hyperurecemia is usually associated with gout and various metabolic arthritis disorders. Limited medications are available to manage such conditions. This study aimed to isolate the triterpenes constituent of the plant and to assess xanthine oxidase (XO) inhibitory and antihyperuricemic activities of  Tribulus arabicus  ethanolic extract, its fractions and the isolated compound using  in vitro and in vivo  approaches.    Methods  The ethanolic extract, fractions; n-hexane, chloroform and n-butanol and the isolated compound (ursolic acid) were evaluated  in vitro  for their XO inhibitory activity. Those that demonstrated significant activity were further evaluated for their antihyperuricemic activity on potassium oxonate-induced hyperuricemia in mice.    Results  The ethanolic extract was found to be safe up to 5000 mg/kg. The extract and its n-hexane fraction exhibited significant inhibitory activity on XO, whilst only a modest reduction in the enzymatic activity was noticed with n-butanol and chloroform fractions. Furthermore, administration of the ethanolic extract at low and high doses significantly reduced serum urate levels in mice by 31.1 and 64.6% respectively. The isolated active constituent, ursolic acid, showed potent XO inhibition activity (Half maximal inhibitory concentration, IC 50  = 10.3 μg/mL), and significantly reduced uric acid level  in vivo  by 79.9%. Virtually, the binding mode of ursolic acid with XO was determined using molecular docking simulations.    Conclusions  The activity of the ethanolic extract of  T .  arabicus  and its n- hexane  fraction can be attributed to the isolated compound, ursolic acid. Ursolic acid has good hypouricemic activity and therefore has high potential to be used for the treatment of gout and hyperuricemia-related diseases.

plos one

Antihyperuricemic and xanthine oxidase inhibitory activities of Tribulus arabicus and its isolated compound, ursolic acid: In vitro and in vivo investigation and docking simulations