Comparative effects of quercetin, luteolin, apigenin and their related polyphenols on uric acid production in cultured hepatocytes and suppression of purine bodies-induced hyperuricemia by rutin in mice.

Abstract

Hyperuricemia, the high uric acid (UA) state in blood, has been accepted as an important risk factor for gout. The liver is a main factory of UA production. In the present study, we have examined the effects of three kinds of flavonol and flavones as typical aglycons, i.e., quercetin, luteolin, apigenin, their glycosides and related compounds, on UA productivity in cultured hepatocytes, adopting allopurinol as the positive control drug. Quercetin, luteolin, diosmetin (4'-O-methylluteolin) and apigenin at 10, 30 and 100μM as well as allopurinol at 0.1, 0.3 and 1μM dose-dependently and significantly decreased UA production in the hepatocytes, when compared with 0μM (control). Both rutin (quercetin-3-O-rutinoside) and quercitrin (quercetin-3-O-ramnoside) significantly reduced UA production in the hepatocytes at 100μM. Luteolin glycosides such as orientin (luteolin-8-C-glucoside) and isoorientin (luteolin-6-C-glucoside) exerted no influences on it even at 100μM. Likewise, apigenin glycosides such as vitexin (apigenin-8-C-glucoside) and isovitexin (apigenin-6-C-glucoside) showed no inhibitory effect on it, while apigetrin (apigenin-7-O-glucoside) significantly reduced it at 100μM. In model mice with purine bodies-induced hyperuricemia, allopurinol completely suppressed the hyperuricemia at a dose of 10mg/kg body weight. Rutin suppressed significantly the hyperuricemia at a dose of 300mg/kg body weight, while vitexin showed no significant effect up to 300mg/kg body weight. Thus, rutin (O-glycoside) is demonstrated to be hypouricemic in both cultured hepatocytes and model mice with recently contrived purine bodies-induced hyperuricemia.