Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy

Phytomedicine. 2017 Jul 1:30:28-41. doi: 10.1016/j.phymed.2017.03.003. Epub 2017 Mar 10.

Abstract

Background: Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF.

Purpose: The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats.

Methods: Rats were subjected to UUO and then administered with vehicle, ATG (1 and 3mg/kg/d), or losartan (20mg/kg/d) for 11 consecutive days. The renoprotective effects of ATG were evaluated by histological examination and multiple biochemical assays.

Results: Our results suggest that ATG significantly protected the kidney from injury by reducing tubular dilatation, epithelial atrophy, collagen deposition, and tubulointerstitial compartment expansion. ATG administration dramatically decreased macrophage (CD68-positive cell) infiltration. Meanwhile, ATG down-regulated the mRNA levels of pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ), in the obstructed kidneys. This was associated with decreased activation of nuclear factor κB (NF-κB). ATG attenuated UUO-induced oxidative stress by increasing the activity of renal manganese superoxide dismutase (SOD2), leading to reduced levels of lipid peroxidation. Furthermore, ATG inhibited the epithelial-mesenchymal transition (EMT) of renal tubules by reducing the abundance of transforming growth factor-β1 (TGF-β1) and its type I receptor, suppressing Smad2/3 phosphorylation and nuclear translocation, and up-regulating Smad7 expression. Notably, the efficacy of ATG in renal protection was comparable or even superior to losartan.

Conclusion: ATG could protect the kidney from UUO-induced injury and fibrogenesis by suppressing inflammation, oxidative stress, and tubular EMT, thus supporting the potential role of ATG in renal fibrosis treatment.

Keywords: Arctigenin; Epithelial-mesenchymal transition; Inflammation; Oxidative stress; Renal fibrosis; Transforming growth factor-β1.

MeSH terms

  • Animals
  • Chemokine CCL2 / metabolism
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / drug effects
  • Fibrosis / drug therapy
  • Fibrosis / pathology
  • Furans / pharmacology*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Lignans / pharmacology*
  • Lipid Peroxidation / drug effects
  • Male
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Ureteral Obstruction / complications*
  • Ureteral Obstruction / pathology

Substances

  • Chemokine CCL2
  • Furans
  • Lignans
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Superoxide Dismutase
  • superoxide dismutase 2
  • arctigenin