Ao Li1, Xiaoxun Zhang2, Mao Shu2, Mingjun Wu3, Jun Wang2, Jingyao Zhang2, Rui Wang4, Peng Li5, Yitao Wang6. 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.
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.
Authors: Philip Chiu-Tsun Tang; Alex Siu-Wing Chan; Cai-Bin Zhang; Cristina Alexandra García Córdoba; Ying-Ying Zhang; Ka-Fai To; Kam-Tong Leung; Hui-Yao Lan; Patrick Ming-Kuen Tang Journal: Front Med (Lausanne) Date: 2021-02-25