期刊
PHYTOMEDICINE
卷 30, 期 -, 页码 28-41出版社
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.phymed.2017.03.003
关键词
Arctigenin; Renal fibrosis; Inflammation; Transforming growth factor-beta 1; Oxidative stress; Epithelial-mesenchymal transition
资金
- National Natural Science Foundation of China [81001675]
- Macao Science and Technology Development Fund [007/2014/AMJ]
- Research Committee of the University of Macau [MYRG2014-00089-ICMS-QRCM]
- Chongqing Natural Science Foundation [cstc2014jcyjA10030]
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 3 mg/kg/d), or losartan (20 mg/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-alpha(TNF-alpha), interleukin-1 beta(IL-1 beta), and interferon-gamma(IFN-gamma), in the obstructed kidneys. This was associated with decreased activation of nuclear factor kappa B (NF-kappa B). 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-beta 1 (TGF-beta 1) 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. (C) 2017 Elsevier GmbH. All rights reserved.
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