期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 68, 期 1, 页码 14-25出版社
WILEY-BLACKWELL
DOI: 10.1111/jphp.12492
关键词
hyperuricemic; morin phospholipid complex; renal organic ion transporter; self-nanoemulsifying drug delivery system; xanthine oxidase
资金
- National Basic Research Program of China (973 Program) [2013CB932504]
- National S & T Major Project of China [2012ZX09304004001]
ObjectivesThis study aimed to compare the biodistribution and hypouricemic efficacy of morin and morin-phospholipid complex loaded self-nanoemulsifying drug delivery systems (MPC-SNEDDS), as well as to explore their therapeutic mechanisms. MethodsWe studied the biodistribution of morin and MPC-SNEDDS after they were orally administered to rats. The hypouricemic efficacy and the therapeutic mechanisms of morin and MPC-SNEDDS were evaluated using potassium oxonate-induced hyperuricemic model in rats. Key findingsWith enhanced morin concentration in liver and kidney, oral delivery of MPC-SNEDDS exhibited significantly stronger urate-lowering effect in hyperuricemic rats than morin. The hypouricemic efficacy of morin was due to reduced production of uric acid via inhibiting the mRNA expression of hepatic xanthine dehydrogenase/xanthine oxidase (XDH/XO), as well as decreased urate reabsorption via modulating the alteration of mRNA levels of glucose transporter (mGLUT9), renal organic anion transporter 1 (mOAT1) and uric acid transporter (mURAT1). MPC-SNEDDS dually inhibited mRNA expression and activity of hepatic XDH/XO and restored the dysregulation of renal mGLUT9, mOAT1 and mURAT1, contributing to its superior urate-lowering efficacy. ConclusionThe results demonstrated the great potential of MPC-SNEDDS as an alternative oral strategy for active agents in treating hyperuricemia.
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