Gout occurs in individuals who have high serum uric acid levels, in response to precipitation of monosodium urate monohydrate crystals in various tissues, followed by an inflammatory response. 1) The essence of the prevention and treatment of gout is antihyperuricemic therapy, either by uricosuric drugs or by xanthine oxidase (XOD) inhibitors. Allopurinol, an XOD inhibitor which is structurally related to xanthine, binds tightly to the active site of XOD thus causes inhibition on XOD. Allopurinol is used to treat gout for more than 40 years and remains a cornerstone in the therapy of primary and secondary hyperuricemia. 2-7) However, the most common adverse effects of allopurinol are gastrointestinal distress, hypersensitivity reactions, 8) and renal toxicity. 9) Thus, new alternatives with an increased therapeutic activity and less side effects are desired.Dietary flavonoids have been attracted attention because of their potential beneficial effects on human health. The structural components common to these molecules include two benzene rings on either side of a 3-carbon ring (Table 1). 10) Multiple combinations of hydroxyl groups, sugars, oxygens, and methyl groups attached to these structures create the various classes of flavonoids: flavanols, flavanones, flavones, flavanonol, flavan-3-ols (catechins), anthocyanins, and isoflavones. 11) Flavonoids are well known to possess antiviral, antiallergic, antiplatelet, antiinflammatory, antitumor and antioxidant activities. 12-15) Catechin and its derivatives, oligomeric proanthocyanidins, quercetin and quercetin chalcone, Ginkgo flavone glycosides, silymarin, and others can be utilized in preventative and treatment protocols for cardiovascular disease, cancer, inflammatory conditions, asthma, periodontal disease, liver disease, cataracts and macular degeneration. 16,17) Hyperuricemia is a risk factor for the disorder metabolic syndrome and increased cardiovascular disease, and the mechanisms involve inflammation and generation of oxidative stress in the vasculature. 18) Thus, the antiinflammatory and antioxidant activities of flavonoids might bring benefit for hyperuricemia and its complications. In addition, the flavonoids have increasingly aroused interest recently for their hypouricemic action in hyperuricemic animal models. [19][20][21] In the present study, we have explored hypouricemic actions from 15 flavonoids including quercetin, morin, myricetin, kaempferol, icariin, apigenin, luteolin, baicalin, silibinin, naringenin, formonoetin, genistein, puerarin, daidzin and naringin dihydrochalcone in a hyperuricemic animal model induced by potassium oxonate. We have also studied the effects of six most active compounds on serum and liver uric acid levels in normal mice. The effects on liver XOD activities were further examined in animals.
MATERIALS AND METHODSMaterials Quercetin, morin, myricetin, kaempferol, icariin, apigenin, luteolin, baicalin, silibinin, naringenin, formonoetin, genistein, puerarin, daidzin and naringin dihydrochalcone were obtained commerci...
