Alpha-asarone relieves nasal inflammation, epithelial barrier damage, and mitochondrial damage in allergic rhinitis by inhibiting mitochondrial ROS via the SIRT1/PGC-1α pathway.

Allergic rhinitis (AR), a chronic inflammatory disease characterized by nasal congestion, sneezing, itching, and rhinorrhea, significantly impairs the quality of life for those affected. Current treatments have limitations due to adverse effects, highlighting the urgent need for novel therapeutic alternatives. This study investigates the protective effects of α-asarone (ASA) on nasal inflammation and epithelial barrier damage in AR, focusing on its modulation of mitochondrial reactive oxygen species (mtROS) via the SIRT1/PGC-1α pathway. Herein, a murine model of AR was established using ovalbumin (OVA) sensitization. ASA ameliorated AR symptoms, reduced IgE, histamine, and nasal mucosal inflammation in mice. It restored tight junction proteins and mitochondrial function markers in the nasal mucosa. In vitro, ASA pretreatment of IL-4/IL-13 challenged human nasal epithelial cells (HNEpCs) suppressed pro-inflammatory cytokines, preserved epithelial barrier integrity, mtROS, and maintained mitochondrial function. Mechanistically, ASA's protective effects were mediated by mtROS inhibition. Using a SIRT1 inhibitor (EX527) and a PGC-1α activator (ZLN005), it was demonstrated that ASA upregulates SIRT1 to promote PGC-1α deacetylation, thereby suppressing mtROS, restoring mitochondrial function, and alleviating nasal inflammation and epithelial barrier damage. SIRT1 inhibition markedly reduced ASA therapeutic effects, highlighting the critical role of the SIRT1/PGC-1α pathway. These results indicate that ASA mitigates nasal inflammation and epithelial barrier damage in AR by suppressing mtROS via the SIRT1/PGC-1α pathway. As a natural agent, ASA presents a promising AR treatment alternative with potentially fewer side effects than conventional therapies.