Flavonoids of Cynara scolymus Possess Potent Xanthinoxidase Inhibitory Activity in vitro but are Devoid of Hypouricemic Effects in Rats after Oral Application

Abstract

Artichoke (Cynara scolymus L.) leaves have been historically used for the treatment of hyperuricemia and gout, however whether artichoke is truly efficacious for this indication, is still a matter of debate. Thus, the goal of the present study was first to examine the xanthine oxidase (XO) inhibitory activity of an artichoke leaf extract (ALE) and some of its main compounds in vitro and then further test potentially active substances for possible hypouricemic effects using an in vivo rat model. The in vitro study showed that ALE inhibited XO with only minimal inhibitory action (< 5 %) at 100 μg/mL. However, when selected compounds were tested, the caffeic acid derivatives revealed a weak XO inhibitory effect with IC₅₀ > 100 μM. From the tested flavones the aglycone luteolin potently inhibited XO with an IC₅₀ value of 1.49 μM. Luteolin 7-O-glucoside and luteolin 7-O-glucuronide showed lower XO inhibition activities with IC₅₀ values of 19.90 μM and 20.24 μM, respectively. However, oral administration of an aqueous ALE, luteolin, and luteolin 7-O-glucoside did not produce any observable hypouricemic effects after acute oral treatment in potassium oxonate-treated rats. After intraperitoneal injection of luteolin a decrease in uric acid levels was detected suggesting that the hypouricemic effects of luteolin are due to its original form rather than its metabolites produced by the gut flora. In conclusion, an aqueous ALE, caffeic acid derivatives and flavones exerted XO inhibitory effects in vitro but a hypouricemic activity could not be confirmed after oral administration.

Abbreviations

ALE:Artichoke leaf extract

CMC-Na:carboxymethylcellulose sodium salt

DAD:photodiode array detector

PO:Potassium oxonate

RP-HPLC:reverse phase high performance liquid chromatography

XO:xanthine oxidase

Key words

Artichoke - Cynara scolymus - Asteraceae - xanthine oxidase - uric acid - hypouricemic - gout - inhibition - flavones - caffeic acid derivatives - potassium oxonate

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