Abstract
The potent anti-hyperuricemia activities of Fructus Gardenia Extract (FGE) have been well reported. The aim of this study was to evaluate the uricosuric and nephro-protective effects of FGE and explore its possible mechanisms of action in oxonate-induced hyperuricemic mice. FGE was orally administered to hyperuricemic and normal mice for 1 week. Serum and urinary levels of uric acid, creatinine and blood urea nitrogen (BUN), and fractional excretion of uric acid (FEUA) were measured. The mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), ATP-binding cassette, subfamily G, 2 (mABCG2), organic anion transporter 1 (mOAT1), mOAT3, oncoprotein induced transcript 3 (mOIT3), organic cation/carnitine transporters in the kidney were analyzed. Simultaneously, Tamm-Horsfall glycoprotein (THP) levels in urine and kidney were detected. FGE significantly reduced serum urate levels and increased urinary urate levels and FEUA in hyperuricemic mice. It could also effectively reverse oxonate-induced alterations in renal mURAT1, mGLUT9, mOAT1 and mOIT3 expressions, as well as THP levels, resulting in the enhancement of renal uric acid excretion. Moreover, FGE decreased serum creatinine and BUN levels, and up-regulated expression of organic cation/carnitine transporters, improving renal dysfunction in this model. Furthermore, FGE decreased renal mABCG2 expressions in hyperuricemic mice, contributing to its beneficial actions. However, further investigation is needed in clinical trials of FGE and its bioactive components.
Highlights
Hyperuricemia, a key risk factor for the development of gout, has been involved in many diseases such as renal dysfunction, cardiovascular diseases, hypertension, hyperlipidemia, diabetes and metabolic syndrome [1,2]
Serum uric acid levels in hyperuricemic animals were significantly lowered by the treatment of Fructus Gardenia Extract (FGE) at 139, 278 and mg/kg in a dose-dependent manner
Expressions of mOIT3 associated with alternations of Tamm-Horsfall glycoprotein (THP) concentrations were firstly explored in oxonate-induced hyperuricemic mouse kidneys, which could be restored by FGE treatment
Summary
Hyperuricemia, a key risk factor for the development of gout, has been involved in many diseases such as renal dysfunction, cardiovascular diseases, hypertension, hyperlipidemia, diabetes and metabolic syndrome [1,2]. Urate transport-related proteins, such as organic anion transporters involved in renal urate secretion and re-absorption, play a pivotal role in maintaining urate homeostasis in vivo [4,5]. Some organic anion transpoters, such as urate transporter 1 (URAT1, SLC22A12) located at the apical membranes, have been reported to be responsible for proximal tubule transport of uric acid, accounting for urate re-absorption [7]. Glucose transporter 9 (GLUT9, SLC2A9) has two splice variants, both of which have been proposed to mediate urate re-absorption [8]. The two splice variants differ only in the length of their amino-terminal cytoplasmic domains, locating at the basolateral (hGLUT9) and apical sides (hGLUT9△N) of proximal convoluted tubules, respectively [9,10].
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