LAUSR

ABSTRACT Reactive oxygen species (ROS) and epithelial–mesenchymal transition (EMT) play a critical role in transforming growth factor (TGF)‐&bgr;1‐mediated fibrotic airway remodeling in asthma. Polydatin (PD) is a small natural molecule in Chinese medicine; it is isolated from Polygonum cuspidatum and has antioxidative properties. In this study, we aimed to determine whether PD was protective against ROS‐induced pulmonary fibrosis in asthma. Ovalbumin (OVA) was used to induce asthma in a mouse model that was treated with or without PD. We also created nuclear factor erythroid 2‐related factor 2 (Nrf2) knockdown BEAS‐2B cells and investigated whether PD reversed TGF‐&bgr;1‐induced pulmonary epithelial cell EMT by promotion of Nrf2‐mediated antioxidation. Immunofluorescence showed that ROS and TGF‐&bgr;1 expression was significantly increased in lung tissue from the OVA‐induced asthma model. PD treatment inhibited activity of ROS and TGF‐&bgr;1. Immunohistochemistry showed that PD treatment decreased OVA‐induced lung ROS, TGF‐&bgr;1 expression and fibroblasts. Western blotting showed that PD treatment reversed OVA‐induced NADPH oxidase (NOX)1/4 expression by promoting Nrf2‐mediated heme oxygenase‐1 and NADPH dehydrogenase (quinone)‐1 expression. PD treatment suppressed OVA‐induced EMT and lung fibroblast protein expression in lung tissue. Nrf2 downregulation suppressed the protective effect of PD by promoting TGF‐&bgr;1‐induced ROS and EMT and accumulation of extracellular‐matrix‐related protein. All these data indicate that PD has potential therapeutic effects in asthma by promoting Nrf2‐mediated antioxidation.