Acupuncture Alleviates Allergic Rhinitis by Activating the AMPK / PGC ‐1α Pathway to Attenuate Mitochondrial Oxidative Stress and Restore Epithelial Barrier Function

ABSTRACT This study aims to elucidate the molecular mechanisms underlying the therapeutic effects of acupuncture in allergic rhinitis (AR), with a focus on its mechanistic pathways. Experimentally, an ovalbumin (OVA)‐induced AR mouse model was established to evaluate the frequency of sneezing and nasal rubbing, histopathological changes in nasal tissue (via H&E staining), and the concentrations of IL‐13, IL‐4, and IL‐5 in serum and nasal lavage fluid (NALF). Network pharmacology analysis was conducted to identify potential acupuncture targets for AR, and a protein–protein interaction (PPI) network was constructed. Subsequent Gene Ontology (GO) functional annotation and KEGG pathway enrichment analyses were performed to elucidate the biological functions and signalling pathways of the target genes. An inflammatory cell model was also developed by stimulating human nasal epithelial cells (HNECs) with IL‐4; these cells were subsequently transfected with AMPKα plasmids or treated with the AMPK inhibitor Dorsomorphin to examine changes in mitochondrial reactive oxygen species (mtROS), ATP production, mitochondrial ultrastructure, and expression of AMPK/PGC‐1α‐related genes and proteins. Dorsomorphin was administered to OVA‐induced AR mice to further evaluate the role of AMPK signalling in acupuncture‐mediated protection. In the murine AR model, acupuncture alleviated pathological damage in nasal tissues, restored the mucosal barrier, and reduced inflammatory cytokine levels in both nasal mucosal tissues and nasal lavage fluid. Network pharmacology analysis suggests that the key protein targets of acupuncture in treating AR (such as PRKAA1, IL‐6, IL‐4) and the main enriched signalling pathways are mainly related to mitochondrial oxidative stress and immune inflammation. In a cellular inflammation model, overexpression of AMPK partially mimicked the therapeutic effect of acupuncture. AMPK activation safeguarded mitochondrial integrity and function by reducing mtROS and upregulating the downstream signalling molecules PGC‐1α, NRF1, and TFAM. Furthermore, Dorsomorphin reversed the protective effects of acupuncture in AR mice. Acupuncture alleviates AR symptoms in OVA‐induced murine models by activating the AMPK/PGC‐1α signalling pathway in nasal mucosal epithelial cells.