Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-κB-mediated inflammatory genes expression

Cytokine. 2013 Mar;61(3):970-7. doi: 10.1016/j.cyto.2013.01.008. Epub 2013 Feb 20.

Abstract

Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n=8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mgkg(-1)d(-1), p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n=8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-κB activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-α, MCP-1 and ICAM-1 in kidney tissues. The α1-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-α, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NF-κB mediated inflammatory genes expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / blood
  • Albuminuria / complications
  • Albuminuria / drug therapy
  • Albuminuria / pathology
  • Animals
  • Biomarkers / blood
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / genetics
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Gene Expression Regulation* / drug effects
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / genetics*
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / genetics
  • Kidney Diseases / blood
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / genetics*
  • Male
  • NF-kappa B / metabolism*
  • Podocytes / drug effects
  • Podocytes / metabolism
  • Podocytes / pathology
  • Podocytes / ultrastructure
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / pharmacology
  • Saponins / therapeutic use*
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Biomarkers
  • Chemokine CCL2
  • Collagen Type IV
  • NF-kappa B
  • RNA, Messenger
  • Saponins
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • astragaloside A