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Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy
Li, Ao1,2; Zhang, Xiaoxun1; Shu, Mao1; Wu, Mingjun3; Wang, Jun1; Zhang, Jingyao1; Wang, Rui1; Li, Peng2; Wang, Yitao2
2017-07
Source PublicationPHYTOMEDICINE
ISSN0944-7113
Volume30Pages:28-41
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 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 atrophycollagen 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.

KeywordArctigenin Renal Fibrosis Inflammation Transforming Growth Factor-beta 1 Oxidative Stress Epithelial-mesenchymal Transition
DOIhttp://doi.org/10.1016/j.phymed.2017.03.003
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPlant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS SubjectPlant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000402491000004
PublisherELSEVIER GMBH, URBAN & FISCHER VERLAG
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWang, Rui; Li, Peng; Wang, Yitao
Affiliation1.College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
3.Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Li, Ao,Zhang, Xiaoxun,Shu, Mao,et al. Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy[J]. PHYTOMEDICINE,2017,30:28-41.
APA Li, Ao.,Zhang, Xiaoxun.,Shu, Mao.,Wu, Mingjun.,Wang, Jun.,...&Wang, Yitao.(2017).Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy.PHYTOMEDICINE,30,28-41.
MLA Li, Ao,et al."Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy".PHYTOMEDICINE 30(2017):28-41.
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