Hypouricemic Action of Scopoletin Arising from Xanthine Oxidase Inhibition and Uricosuric Activity

Abstract

Scopoletin exhibited an immediate and dose-dependent hypouricemic effect after intraperitoneal administration (50, 100, 200 mg/kg) in hyperuricemic mice induced by potassium oxonate; however, it did not affect the serum uric acid level in normal mice at the tested doses. For exploring the involved mechanisms of action of scopoletin, potential inhibitory effects on xanthine oxidase and possible uricosuric effects were investigated. Scopoletin (50, 100, 200 mg/kg) significantly inhibited the activity of xanthine oxidase in liver homogenates of hyperuricemic mice although it only showed a relatively weak, albeit competitive-type, inhibition of xanthine oxidase in a commercial assay. Furthermore, a potent uricosuric effect of scopoletin (100, 200 mg/kg) was ascertained. These results demonstrated for the first time that scopoletin exhibits, hypouricemic activities through decreasing uric acid production and as well as a uricosuric mechanism.

References

• 1 Lawrence R C, Helmick C G, Arnett F C. et al . Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States.  Arthritis Rheum. 1998;  41 778-99
• 2 Roubenoff R. Gout and hyperuricemia.  Rheum Dis Clin North Am. 1990;  16 539-50
• 3 Farah M H, Samuelsson G. Pharmacologically active phenylpropanoids from Senra incana .  Planta Medica. 1992;  58 14-8
• 4 Silvan A M, Abad M J, Bermejo P, Sollhuber M, Villar A. Anti-inflammatory activity of coumarins from Santolina oblongifolia .  J Nat Prod. 1996;  59 1183-5
• 5 Muschietti L, Gorzalczany S, Ferraro G, Acevedo C, Martino V. Phenolic compounds with anti-inflammatory activity from Eupatorium buniifolium .  Planta Medica. 2001;  67 743-4
• 6 Chang W S, Chiang Y H, Lu F J, Chang H C. Inhibitory effects of phenolics on xanthine oxidase.  Anticancer Res. 1994;  14 501-6
• 7 Chang W S, Chiang H C. Structure-activity relationship of coumarins in xanthine oxidase inhibition.  Anticancer Res. 1995;  15 1969-73
• 8 Kong L D, Zhou J, Wen Y L, Li J M, Cheng C HK. Aesculin possesses potent hypouricemic action in rodents but is devoid of xanthine oxidase /dehydrogenase inhibitory activity.  Planta Medica. 2002;  68 175-8
• 9 Wright J D, Printo A B. Clinical manifestations and treatment of gout.  Prim Care Update Ob/Gyns. 2003;  10 19-23
• 10 Dan T, Koga H, Onuma E, Tanaka H, Sato H, Aoki B. The activity of AA-193, a new uricosuric agent, in animals.  Adv Exp Med Biol. 1989;  253A 301-8
• 11 Hall I H, Scoville J P, Reynolds D J, Simlot R, Duncan P. Substituted cyclic imides as potential anti-gout agents.  Life Sci. 1990;  46 1923-7
• 12 Huh K, Yamamoto I, Gohda E, Iwata H. Tissue distribution and characteristics of xanthine oxidase and allopurinol oxidizing enzyme.  Jap J Pharmacol. 1976;  26 719-24
• 13 Noro T, Oda Y, Miyase T, Ueno A, Fukushima S. Inhibition of xanthine oxidase from the flowers and buds of Daphne genkwa .  Chem Pharm Bull. 1983;  31 3984-7