Abstract

BackgroundAstragalus membranaceus, a traditional Chinese medicine (TCM), has been widely used in the treatment of chronic kidney disease (CKD) in China. Astragaloside IV is one of the major compounds of Astragalus membranaceus. Recent research has shown that astragaloside IV demonstrates pharmacological effects, such as anti-inflammatory, anti-fibrotic and anti-oxidative stress activities. Our aim was to investigate the effects of astragaloside IV on indoxyl sulfate (IS)-induced kidney injury in vivo, and to study the underlying mechanism.MethodsForty C57BL/6 mice with ½ nephrectomy were divided into four groups: control group (n = 10), IS group (n = 10), IS plus 10 mg/kg of astragaloside IV group (n = 10) and IS plus 20 mg/kg of astragaloside IV group (n = 10). IS intraperitoneal injection and astragaloside IV treatment were administered continuously for 1 month. Next, the blood urea nitrogen (BUN) level, serum IS level, tubulointerstitial injury, renal oxidative stress and inflammatory injury were assessed.ResultsThe IS intraperitoneal injection mouse group showed increasing levels of serum IS, BUN, tubulointerstitial injury, renal oxidative stress and inflammatory injury. Astragaloside IV treatment couldn’t reduce the serum IS level or renal nuclear factor-κB and interleukin-1β levels. However, 20 mg/kg astragaloside IV treatment reduced the BUN level and significantly attenuated IS-induced tubulointerstitial injury. Renal oxidative stress was decreased by the administration of astragaloside IV.ConclusionsThese results suggest that astragaloside IV prevents IS-induced tubulointerstitial injury by ameliorating oxidative stress and may be a promising agent for the treatment of uremia toxin-induced injury.

Highlights

  • Astragalus membranaceus, a traditional Chinese medicine (TCM), has been widely used in the treatment of chronic kidney disease (CKD) in China

  • The level of serum blood urea nitrogen (BUN) was significantly increased in indoxyl sulfate (IS) intraperitoneal injection group mice (P < 0.001)

  • The level of BUN of IS intraperitoneal injection mice was significantly decreased after 20 mg/kg of astragaloside IV treatment (P = 0.048)

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Summary

Introduction

Astragalus membranaceus, a traditional Chinese medicine (TCM), has been widely used in the treatment of chronic kidney disease (CKD) in China. Our aim was to investigate the effects of astragaloside IV on indoxyl sulfate (IS)-induced kidney injury in vivo, and to study the underlying mechanism. In chronic kidney disease (CKD), metabolic changes, disorders of gut microflora and impaired urinary excretion of metabolites lead to the accumulation of uremic toxins in the body [1]. Indoxyl sulfate (IS), one of the most extensively studied uremic toxins, has been increasingly recognized as an important contributor to kidney and heart dysfunction [2,3,4]. Dialysis is not powerful enough to remove protein-bound uremic toxins alone [7, 8]. Identifying effective measures to reduce IS-induced injury is of significant value

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