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.

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'--methylluteolin) and apigenin at 10, 30 and 100 μM as well as allopurinol at 0.1, 0.3 and 1 μM dose-dependently and significantly decreased UA production in the hepatocytes, when compared with 0 μM (control). Both rutin (quercetin-3--rutinoside) and quercitrin (quercetin-3--ramnoside) significantly reduced UA production in the hepatocytes at 100 μM. Luteolin glycosides such as orientin (luteolin-8--glucoside) and isoorientin (luteolin-6--glucoside) exerted no influences on it even at 100 μM. Likewise, apigenin glycosides such as vitexin (apigenin-8--glucoside) and isovitexin (apigenin-6--glucoside) showed no inhibitory effect on it, while apigetrin (apigenin-7--glucoside) significantly reduced it at 100 μM. In model mice with purine bodies-induced hyperuricemia, allopurinol completely suppressed the hyperuricemia at a dose of 10 mg/kg body weight. Rutin suppressed significantly the hyperuricemia at a dose of 300 mg/kg body weight, while vitexin showed no significant effect up to 300 mg/kg body weight. Thus, rutin (-glycoside) is demonstrated to be hypouricemic in both cultured hepatocytes and model mice with recently contrived purine bodies-induced hyperuricemia.