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

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

Author information

1
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
2
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.
3
Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.
4
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China. Electronic address: wangrx1022@163.com.
5
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China. Electronic address: pengli@umac.mo.
6
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.

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

PMID:
28545667
DOI:
10.1016/j.phymed.2017.03.003
[Indexed for MEDLINE]

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