Astragaloside IV prevents acute kidney injury in two rodent models by inhibiting oxidative stress and apoptosis pathways

Apoptosis. 2013 Apr;18(4):409-22. doi: 10.1007/s10495-013-0801-2.


Oxidative stress and apoptosis play key role in the pathogenesis of acute kidney injury (AKI). We hypothesize that Astragaloside IV(AS-IV) prevents AKI through inhibiting oxidative stress and apoptosis. The rats were divided into sham control, saline-,vehicle-, or AS-IV-treated groups. AS-IV (20 mg/kg) was orally administered once daily to the rats for 7 consecutive days before terminating the experiments. In ischemia-induced AKI model, experimental rats were subjected to bilateral clamping of the renal arteries for 45 min, followed by reperfusion for 24 h. In contrast-induced AKI model, iopamidol (2.9 g iodine/kg) was administered intravenously into the rats. Renal function, histopathology, oxidative stress and apoptosis were evaluated in these models. Pretreatment with AS-IV significantly decreased blood urea nitrogen, serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels, as well as urinary kidney injury molecule-1 level and tubular injury. AS-IV also reduced oxidative stress and tubular cell apoptosis. The p38 mitogen-activated protein kinase phosphorylation and caspase-3 activity were elevated in kidney tissues from AKI rats, accompanied by an increase in Bax expression and a decrease in Bcl-2 expression at mRNA and protein levels. These changes were prevented by AS-IV pretreatment. Therefore, AS-IV can be developed as a novel therapeutic approach to prevent AKI through targeting inhibition of oxidative stress and apoptosis pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / prevention & control*
  • Acute Kidney Injury / surgery
  • Acute-Phase Proteins
  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Adhesion Molecules / urine
  • Cystatin C / blood
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Ischemia / surgery
  • Kidney / blood supply*
  • Kidney / drug effects
  • Kidney / surgery
  • Kidney Function Tests
  • Lipocalin-2
  • Lipocalins / blood
  • Male
  • Models, Animal
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / blood
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Renal Artery / surgery
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control
  • Saponins / pharmacology
  • Saponins / therapeutic use*
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Acute-Phase Proteins
  • Cell Adhesion Molecules
  • Cystatin C
  • Drugs, Chinese Herbal
  • Havcr1protein, rat
  • Lcn2 protein, rat
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Saponins
  • Triterpenes
  • astragaloside A
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3