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.
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.
Phytomedicine. 2017 Jul 1;30:28-41. doi: 10.1016/j.phymed.2017.03.003. Epub 2017 Mar 10.
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.
肾间质纤维化（TIF）通常是多种进行性损伤的最终结果，导致终末期肾病。目前，延缓肾 TIF 发展的治疗药物很少。
本研究旨在评估牛蒡子苷（ATG）在保护肾脏免受单侧输尿管梗阻（UUO）大鼠肾损伤中的作用。ATG 是从牛蒡（Arctium lappa L.）果实中提取的木脂素成分。
大鼠接受 UUO 手术，然后连续 11 天给予载体、ATG（1 和 3mg/kg/d）或氯沙坦（20mg/kg/d）。通过组织学检查和多种生化测定评估 ATG 的肾保护作用。
我们的结果表明，ATG 通过减少肾小管扩张、上皮萎缩、胶原沉积和肾小管间质腔扩张，显著保护肾脏免受损伤。ATG 给药可显著减少巨噬细胞（CD68 阳性细胞）浸润。同时，ATG 下调了阻塞肾脏中促炎趋化因子单核细胞趋化蛋白-1（MCP-1）和细胞因子（包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和干扰素-γ（IFN-γ））的 mRNA 水平，与核因子κB（NF-κB）的激活减少有关。ATG 通过增加肾脏锰超氧化物歧化酶（SOD2）的活性来减轻 UUO 诱导的氧化应激，从而降低脂质过氧化水平。此外，ATG 通过减少转化生长因子-β1（TGF-β1）及其 I 型受体的丰度，抑制 Smad2/3 磷酸化和核转位，上调 Smad7 表达，抑制肾小管上皮-间充质转化（EMT）。值得注意的是，ATG 在肾脏保护方面的疗效与氯沙坦相当，甚至优于氯沙坦。
ATG 可通过抑制炎症、氧化应激和肾小管 EMT 来保护肾脏免受 UUO 诱导的损伤和纤维化，这支持了 ATG 在肾脏纤维化治疗中的潜在作用。
