Dietary Quercetin-3-Glucuronide Mitigates Oxidative Stress, Inflammation, and Fibroblast Transition by Regulating Nrf2 and Autophagy in Pulmonary Fibrosis

Pulmonary fibrosis involves oxidative stress, inflammation, and fibroblast-to-myofibroblast transition (FMT). Quercetin-3-glucuronide (Q3G) exhibits antioxidant and anti-inflammatory properties; however, its antifibrotic effects remain unclear. This study aimed to investigate the protective role of Q3G in epithelial injury-induced fibroblast activation, with a focus on nuclear factor erythroid 2–related factor 2 (Nrf2) and autophagy regulation. First, the decreased expressions of Nrf2 and an autophagy marker LC3 were detected in human emphysema compared with normal subjects. Further results demonstrated Q3G enhanced both coexpressions, while suppressing reactive oxygen species (ROS), interleukin (IL)-1β, IL-6, and extracellular matrix (ECM) deposition. The protective effects of Q3G were significantly reversed by Nrf2 silencing or autophagy inhibition. The Q3G-induced colocalization of Nrf2 and LC3 suggests a functional coupling between these pathways, which contributes to redox homeostasis and the attenuation of fibrosis. These findings indicate that Q3G mitigates oxidative stress, inflammation, and FMT via the coordinated activation of Nrf2 and autophagy, highlighting its therapeutic potential in pulmonary fibrosis.