Xanthine oxidase inhibition and antioxidant activity of an artichoke leaf extract (Cynara scolymus L.) and its compounds

Gout is a disease characterized by elevated levels of uric acid in body fluids. This hyperuricemia results in the deposition of urate crystals in tissue, especially joints. The uric acid deposition initiates an inflammation process involving the release of reactive oxygen species. The common treatments of gout are the use of anti-inflammatory agents to relieve the symptoms of the disease and xanthine oxidase (XO) inhibitors to block the synthesis of uric acid. The most common xanthine oxidase inhibitor is allopurinol. However, its use is limited by unwanted side effects such as hypersensitivity problems. Therefore, alternatives are required.;Artichoke leaves (Cynara scolymus L.) have been used traditionally by the Eclectic physicians as a diuretic and depurative for the treatment of gout. The major compounds in artichoke leaves are phenolic compounds such as caffeoylquinic acids and flavonoids. These phenolic compounds have shown xanthine oxidase inhibitory activity and antioxidant activity in vitro and in vivo. Therefore, the goal of the present study was to examine the xanthine oxidase inhibitory activity and antioxidant activity of the artichoke extract, and its main compounds in vitro and in vivo.;The in vitro study showed that the extract as well as caffeoylquinic acids showed only a weak XO inhibition, whereas flavonoids (flavone and flavonols) had a highly inhibitory effect on XO. Luteolin had the highest XO inhibition effect. This significant inhibition of XO by the flavonoids in vitro suggested that they may suppress the production of uric acid in vivo. However, the in vivo study showed that oral administration of the artichoke extract, caffeoylquinic acids, and flavonoids could not decrease the serum urate levels in oxonate-treated rats.;The antioxidant activities of the artichoke extract and its phenolic compounds were determined using the oxygen radical absorbance capacity assay (ORAC). The results showed that the artichoke extract and its compounds elicited an antioxidant activity in vitro, however, the compounds again showed no antioxidant activity in vivo.;It was speculated that this lack of effect in vivo from both studies might be due to the absorption, the high first pass effect through intestine and liver, the excretion into urine and bile and the degradation in large intestine. Therefore, the pharmacokinetic of a compound in artichoke was performed in order to explain the in vivo activity.;Pharmacokinetic study of luteolin, the compound which showed the highest XO inhibition in vitro, showed that after oral administration of luteolin, luteolin rapidly absorbed and metabolized in plasma. Additionally, plasma-concentration-time curves of luteolin metabolites revealed secondary peaks. The bioavailability of luteolin was low and the urinary excretion of luteolin and its conjugates did not dominate. This study could explain the lack of XO inhibitory activity and antioxidant activity in vivo. Therefore, it can be concluded that artichoke might be not a useful alternative treatment of gout.