Pterostilbene Ameliorates Nephropathy Injury in Streptozotocin-Induced Diabetic Rats

Pharmacology. 2019;104(1-2):71-80. doi: 10.1159/000500293. Epub 2019 May 22.

Abstract

Background: Our study investigated the therapeutic role and potential mechanisms of pterostilbene (PS) in diabetic nephropathy (DN) rats.

Methods: DN models were established by high-fat diet after streptozotocin injection. A total of 50 Sprague-Dawley rats were randomly divided into control, DN, PS-treated groups (PS-H, PS-M, PS-L). PS was administered to rats by gavage for 8 weeks at 3 different doses (25, 10, and 5 mg/kg/day). The levels of oxidative stress activity (superoxide dismutase [SOD], malondialdehyde [MDA], glutathione peroxidase [GSH-PX]) and inflammatory factors (tumor necrosis factor [TNF]-α, interleukin (IL)-6, IL-1β, monocyte chemoattractant factor [MCP]-1) were detected by -ELISA. TGF-β, Smad1, and fibronectin (FN) were measured through immunohistochemistry. The relative expressions of phospho-IκBα/IκBα, phospho-IκB kinases (IKK)β/IKKβ, phospho-nuclear factor-κB (NF-κB) p65/NF-κB p65 were detected by western blot.

Results: Compared with DN group, the levels of TNF-α, IL-6, IL-1β, and MCP-1 were decreased in the PS-H group (p < 0.05). Meanwhile, the levels of SOD, MDA, GSH-PX improved in kidney and serum in PS-H groups (p< 0.05). PS also significantly decreased the level of phospho-NF-κB p65 and increased the levels of phospho- IKKβ and phospho-Iκ-Bα (p < 0.05). The results showed that PS treatment decreased TGF-β, Smad1, and FN expressions.

Conclusion: PS had potential therapeutic effects on DN, which may be related to the regulation of NF-κB pathway.

Keywords: Diabetic nephropathy; Inflammation; Nuclear factor-κB signaling; Oxidative stress; Pterostilbene.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / etiology
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / pathology
  • Diet, High-Fat / adverse effects
  • Drug Evaluation, Preclinical
  • Fibronectins / metabolism
  • Humans
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Smad1 Protein / metabolism
  • Stilbenes / administration & dosage*
  • Streptozocin / toxicity
  • Transforming Growth Factor beta / metabolism
  • Treatment Outcome

Substances

  • Fibronectins
  • NF-kappa B
  • Smad1 Protein
  • Smad1 protein, rat
  • Stilbenes
  • Transforming Growth Factor beta
  • pterostilbene
  • Streptozocin