Abstract
Hyperuricemia is associated with a number of pathological conditions such as gout. Lowering of elevated uric acid level in the blood could be achieved by xanthine oxidase inhibitors and inhibitors of renal urate reabsorption. Some natural compounds isolated from herbs used in traditional Chinese medicine have been previously demonstrated to possess xanthine oxidase inhibitory activities. In the present investigation, morin (3,5,7,2′,4′-pentahydroxyflavone), which occurs in the twigs of Morus alba L. documented in traditional Chinese medicinal literature to treat conditions akin to gout, was demonstrated to exert potent inhibitory action on urate uptake in rat renal brush-border membrane vesicles, indicating that this compound acts on the kidney to inhibit urate reabsorption. Lineweaver-Burk transformation of the inhibition kinetics data demonstrated that the inhibition of urate uptake was of a competitive type, with a Ki value of 17.4 μM. In addition, morin was also demonstrated to be an inhibitor of xanthine oxidase. Lineweaver-Burk analysis of the enzyme kinetics indicated that the mode of inhibition was of a mixed type, with Ki and Kies values being 7.9 and 35.1 μM, respectively. Using an oxonate-induced hyperuricemic rat model, morin was indeed shown to exhibit an in vivo uricosuric action, which could explain, in part at least, the observed hypouricemic effect of morin in these rats. The potential application of this compound in the treatment of conditions associated with hyperuricemia was discussed.
Footnotes
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This work was supported by a grant from the Research Grant Council of the Hong Kong Special Administrative Region (Project CUHK 4269/02M), by direct grants from The Chinese University of Hong Kong, and by support through the campus work scheme from United College.
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doi:10.1124/jpet.105.092684.
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ABBREVIATIONS: URAT1, urate-anion transporter 1; morin, 3,5,7,2′,4′-pentahydroxyflavone; BBMV, brush-border membrane vesicle; HPLC, high-performance liquid chromatography.
- Received July 15, 2005.
- Accepted September 14, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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