Abstract

Background Dihydroquercetin (DHQ) is a flavonoid with strong anti-inflammatory and antioxidant effects. However, its protective activity against cigarette smoke-induced ferroptosis in the pathogenesis of chronic obstructive pulmonary disease and its underlying mechanisms remain unclear. Purpose The present study was conducted to investigate the protective role of DHQ in the pathogenesis of COPD in vivo and in vitro . Methods A cigarette smoke-induced COPD mouse model was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). During the modeling process, the mice were intraperitoneally injected with DHQ daily. HBE cells were cultured with CSE with or without pretreatment with DHQ (40, 80 μM) or ML385 (10 μM). Cell viability was assessed by a cell counting kit 8 (CCK-8). The contents of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by MDA and SOD assay kits, respectively, and reactive oxygen species (ROS) generation was detected by DCFH-DA assays. Protein expression levels of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPx4) and nuclear factor erythroid 2-related factor 2 (Nrf2) were measured by western blot . Lipid peroxidation was determined by C11-BODIPY staining. Transmission electron microscopy was used to observe the morphological features of the mitochondria. Results Treatment with DHQ significantly elevated ferroptosis-related protein (SLC7A11 and GPx4) expression in vivo and in vitro . The mRNA levels of SLC7A11 and GPx4 were also increased after DHQ treatment. The excessive MDA and ROS production and depleted SOD activity induced by CSE were reversed by DHQ. DHQ notably reduced the increased lipid peroxidation induced by CSE in HBE cells. In addition, treatment with DHQ attenuated the morphological changes in the