Yu Zhifeng, Fong Wing Ping, Cheng Christopher H K
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
J Pharmacol Exp Ther. 2006 Jan;316(1):169-75. doi: 10.1124/jpet.105.092684. Epub 2005 Sep 16.
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 K(i) value of 17.4 microM. 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 K(i) and K(ies) values being 7.9 and 35.1 microM, 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.
高尿酸血症与许多病理状况相关，如痛风。通过黄嘌呤氧化酶抑制剂和肾尿酸重吸收抑制剂可降低血液中升高的尿酸水平。先前已证明，从传统中药中分离出的一些天然化合物具有黄嘌呤氧化酶抑制活性。在本研究中，桑色素（3,5,7,2',4'-五羟基黄酮）存在于桑科植物桑（Morus alba L.）的嫩枝中，传统中药文献记载其可治疗类似于痛风的病症，研究表明其对大鼠肾刷状缘膜囊泡中的尿酸摄取具有强效抑制作用，表明该化合物作用于肾脏以抑制尿酸重吸收。对抑制动力学数据进行Lineweaver-Burk转换表明，尿酸摄取的抑制为竞争性类型，K(i)值为17.4 microM。此外，桑色素还被证明是一种黄嘌呤氧化酶抑制剂。对酶动力学进行Lineweaver-Burk分析表明，抑制模式为混合型，K(i)和K(ies)值分别为7.9和35.1 microM。使用氧嗪酸钾诱导的高尿酸血症大鼠模型，确实显示桑色素具有体内促尿酸排泄作用，这至少可以部分解释在这些大鼠中观察到的桑色素降尿酸作用。讨论了该化合物在治疗与高尿酸血症相关病症中的潜在应用。
