Peritoneal fibrosis (PF) caused by long-term peritoneal dialysis is closely associated with the epithelialmesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs). Moreover, the antifibrotic role of Arctigenin (Arc) has been reported in several fibrosis disorders. Therefore, the preventive effect of Arc on transforming growth factor-beta 1 (TGF-beta 1)-induced EMT and the underlying mechanisms in HPMCs was investigated in this study. Firstly, the PD model was established by TGF-beta 1 stimulation in cultured HPMCs in vitro, we found that TGF-beta 1 significantly increased the EMT markers (siSMA, vimentin, and fibronectin) and plasminogen activator inhibitor type 1 (PAI-1) expressions, but decreased epithelial marker (E-cadherin). Co-treatment with Arc (10, 20, 40 mu M) ameliorated TGF-beta 1-induced EMT in a dose-dependent manner, and the expression of PAI-1 was also inhibited by Arc, which was abrogated by restoration of PAI-1. Moreover, Arc enhanced the phosphorylated AMP-activated protein kinase (AMPK), but inhibited the phosphorylated hcBci level and nuclear translocation of nuclear factor KB (NF-kappa B) p65 in TGF-beta 1-induced HPMCs. ChIP and Luciferase reporter assays verified that the increased binding capacity of NF-kappa B to the promoter of PAI-1 induced by TGF-beta 1 was reversely attenuated by Arc in HPMCs. However, the effect of Arc on TGF-beta 1-induced NF-kappa B activation, PAI-1 expression and EMT in HPMCs was attenuated by AMPK agonist Compound C. In conclusion, these data demonstrated that Arc suppressed TGF-beta 1-induced EMT by activating the AMPK/NF-kappa B pathway to inhibit PAI-1 expression in HPMCs. Therefore, Arc might act as a potential therapeutic agent for PD treatment. (C) 2019 Elsevier Inc. All rights reserved.