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

• Published in: Phytomedicine (Stuttgart) 2017-07, Vol.30, p.28-41
• Main Authors: Li, Ao, Zhang, Xiaoxun, Shu, Mao, Wu, Mingjun, Wang, Jun, Zhang, Jingyao, Wang, Rui, Li, Peng, Wang, Yitao
• Format: Article
• Language: English
• Subjects: Animals; Arctigenin; Chemokine CCL2 - metabolism; Disease Models, Animal; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Fibrosis - drug therapy; Fibrosis - pathology; Furans - pharmacology; Inflammation; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; Kidney Diseases - pathology; Lignans - pharmacology; Lipid Peroxidation - drug effects; Male; NF-kappa B - metabolism; Oxidative stress; Oxidative Stress - drug effects; Rats, Sprague-Dawley; Renal fibrosis; Superoxide Dismutase - metabolism; Transforming growth factor-β1; Tumor Necrosis Factor-alpha - metabolism; Ureteral Obstruction - complications; Ureteral Obstruction - pathology
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2017.03.003

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. 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. 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. 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. 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. [Display omitted]