PMID- 28545667 OWN - NLM STAT- MEDLINE DCOM- 20170912 LR - 20181202 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 30 DP - 2017 Jul 1 TI - Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy. PG - 28-41 LID - S0944-7113(17)30044-2 [pii] LID - 10.1016/j.phymed.2017.03.003 [doi] AB - 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-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interferon-gamma (IFN-gamma), in the obstructed kidneys. This was associated with decreased activation of nuclear factor kappaB (NF-kappaB). 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-beta1 (TGF-beta1) 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. CI - Copyright (c) 2017 Elsevier GmbH. All rights reserved. FAU - Li, Ao AU - Li A AD - 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. FAU - Zhang, Xiaoxun AU - Zhang X AD - College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China. FAU - Shu, Mao AU - Shu M AD - College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China. FAU - Wu, Mingjun AU - Wu M AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. FAU - Wang, Jun AU - Wang J AD - College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China. FAU - Zhang, Jingyao AU - Zhang J AD - College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China. FAU - Wang, Rui AU - Wang R AD - College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China. Electronic address: wangrx1022@163.com. FAU - Li, Peng AU - Li P AD - 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. FAU - Wang, Yitao AU - Wang Y AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China. LA - eng PT - Journal Article DEP - 20170310 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Chemokine CCL2) RN - 0 (Furans) RN - 0 (Lignans) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.15.1.1 (superoxide dismutase 2) RN - U76MR9VS6M (arctigenin) SB - IM MH - Animals MH - Chemokine CCL2/metabolism MH - Disease Models, Animal MH - Epithelial-Mesenchymal Transition/drug effects MH - Fibrosis/drug therapy/pathology MH - Furans/*pharmacology MH - Kidney/drug effects/metabolism/pathology MH - Kidney Diseases/*drug therapy/*metabolism/pathology MH - Lignans/*pharmacology MH - Lipid Peroxidation/drug effects MH - Male MH - NF-kappa B/metabolism MH - Oxidative Stress/drug effects MH - Rats, Sprague-Dawley MH - Superoxide Dismutase/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Ureteral Obstruction/*complications/pathology OTO - NOTNLM OT - Arctigenin OT - Epithelial-mesenchymal transition OT - Inflammation OT - Oxidative stress OT - Renal fibrosis OT - Transforming growth factor-beta1 EDAT- 2017/05/27 06:00 MHDA- 2017/09/13 06:00 CRDT- 2017/05/27 06:00 PHST- 2016/03/28 00:00 [received] PHST- 2016/12/28 00:00 [revised] PHST- 2017/03/09 00:00 [accepted] PHST- 2017/05/27 06:00 [entrez] PHST- 2017/05/27 06:00 [pubmed] PHST- 2017/09/13 06:00 [medline] AID - S0944-7113(17)30044-2 [pii] AID - 10.1016/j.phymed.2017.03.003 [doi] PST - ppublish SO - Phytomedicine. 2017 Jul 1;30:28-41. doi: 10.1016/j.phymed.2017.03.003. Epub 2017 Mar 10.