Constituents and Anti-Hyperuricemia Mechanism of Traditional Chinese Herbal Formulae Erding Granule.

Wugang Zhang,Shilin Yang,Haifang Chen,Wuliang Yang,Wendi Du,Guofeng Li,Chen Zhang,Yulin Feng

doi:10.3390/molecules24183248

Wugang Zhang, Shilin Yang + Show 6 more

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https://doi.org/10.3390/molecules24183248

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Abstract

Erding granule (EDG) is a traditional Chinese medicine that has recently been identified as having anti-hypouricemic effects. However, the active components and underlying mechanism for this new indication have not been elucidated. Therefore, we compared the effects of different EDG extracts (water, 50% ethanol and 95% ethanol) on serum uric acid concentrations in the hyperuricemia model mouse. We also analyzed the constituents of different extracts by ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) to observe the variation between the active and inactive products. Extract activity and target site were evaluated by assessing uric acid- and inflammation-suppressing effects along with evaluating ability to regulate the uric acid transporter. The results showed that the 50% ethanol extract (EDG-50) had an obvious serum uric acid concentration lowering effect compared with water (EDG-S) and the 95% ethanol extract (EDG-95). UHPLC-Q-TOF-MS/MS analysis showed that EDG-50 was compositionally different to EDG-S and EDG-95. EDG-50 showed dose-dependent effects on reducing uric acid, suppressing inflammation and regulating uric acid transporters. Moreover, western blot analysis showed that EDG-50 down-regulated GLUT9 and URAT1 expression, and up-regulated OAT1 expression. Therefore, our findings enable the preliminarily conclusion that EDG-50 lowers serum uric acid concentrations, mainly by down-regulating the expression of GLUT9 and URAT1 proteins and up-regulating the expression of OAT1 proteins. This provides a research basis for clinical use of EDG as an anti-hyperuricemic agent.

Highlights

Hyperuricemia is human metabolic disorder resulting from increased uric acid formation and/or reduced uric acid elimination
The serum concentrations of uric acid, creatinine and blood urea nitrogen in mice with hyperuricemia were determined after intervention with different Erding granule (EDG) extracts (EDG-S, EDG-50 and EDG-95)
Compared with the model group (MG), uric acid (UA) and creatinine serum concentrations were decreased in all treatment groups, especially in the AP group (APG) (P < 0.01) and EDG-50 group (50G) (P < 0.05); creatinine and blood urea nitrogen concentrations in the APG were significantly increased (P < 0.01); EDG extracts with different polarity reduced creatinine and blood urea nitrogen, which was slightly significant in the 50G, but not significantly different in the MG

Summary

Introduction

Hyperuricemia is human metabolic disorder resulting from increased uric acid formation and/or reduced uric acid elimination. Elevated serum uric acid concentrations may precipitate gout [1,2] and contribute to cardiovascular disease [3,4], type 2 diabetes mellitus [5], nonalcoholic fatty liver disease [6], and chronic kidney disease [7,8], which can seriously compromise human health. Reducing uric acid production with xanthine oxidase inhibitors and increasing uric acid excretion with diuretics are still the main treatments for lowering serum uric acid concentrations. The discovery of new uric acid-lowering drugs remains of considerable research interest [9,10,11,12].

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