Resveratrol Ameliorates Allergic Rhinitis by Activating SIRT1 to Disrupt the Mitochondrial ROS ‐Inflammation Vicious Cycle

ABSTRACT Allergic rhinitis (AR) is a common immune disorder characterised by Th2‐type inflammation and oxidative stress. This study aimed to investigate whether resveratrol (RES) alleviates AR by disrupting the mitochondria‐ROS‐inflammation vicious cycle via activation of silent information regulator 1 (SIRT1). Network pharmacology was employed to predict common targets of RES against AR, and the underlying mechanisms were validated in both cellular and animal models. The results demonstrated that RES significantly suppressed lipopolysaccharide‐ or ovalbumin‐induced intracellular ROS accumulation (reduced by ~45%, p < 0.001), restored mitochondrial membrane potential, promoted macrophage polarisation towards the M2 phenotype, and activated the Nrf2/HO‐1 antioxidant pathway in both macrophages and nasal epithelial cells. These effects were reversed by the SIRT1 inhibitor EX527. In an OVA‐induced AR mouse model, RES treatment markedly alleviated nasal symptoms (sneezing frequency reduced by ~60%, * p < 0.001; nasal rubbing decreased by ~55%, p < 0.001), inflammatory cell infiltration, goblet cell hyperplasia, and mucosal thickening, while also suppressing NF‐κB activation and lipid peroxidation. This study is the first to systematically elucidate that RES mitigates the pathological progression of AR by activating SIRT1, thereby improving mitochondrial function and suppressing oxidative stress and inflammatory responses. Our findings suggest that targeting SIRT1 could represent a novel therapeutic strategy for AR.