Polydatin attenuates reactive oxygen species-induced airway remodeling by promoting Nrf2-mediated antioxidant signaling in asthma mouse model

Reactive oxygen species (ROS) and epithelial-mesenchymal transition (EMT) play a critical role in transforming growth factor (TGF)-beta 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-beta 1-induced pulmonary epithelial cell EMT by promotion of Nrf2-mediated antioxidation. Immunofluorescence showed that ROS and TGF-beta 1 expression was significantly increased in lung tissue from the OVA-induced asthma model. PD treatment inhibited activity of ROS and TGF-beta 1. Immunohistochemistry showed that PD treatment decreased OVA-induced lung ROS, TGF-beta 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-beta 1-induced ROS and EMT and accumulation of extracellular-matrixrelated protein. All these data indicate that PD has potential therapeutic effects in asthma by promoting Nrf2-mediated antioxidation.