OBJECTIVE To explore the intervention effects and potential mechanisms of guanosine on allergic asthma mice models through metabolomics analysis, with its functions in host immune response and metabolic regulation, so as to provide a theoretical basis for the clinical treatment of asthma.

METHODS The study utilized 40 SPF-grade male Balb/c mice, randomly assigned to normal group, model group, positive drug group(montelukast sodium, 1.3 mg·kg⁻¹), low-dose guanosine nucleoside group(Guanosine-L, 15 mg·kg⁻¹), and high-dose guanosine nucleoside group(Guanosine-H, 30 mg·kg⁻¹). An ovalbumin(OVA)-induced allergic asthma mouse model was established. After 7 consecutive days of drug administration, coughing and wheezing indices, lung function, and lung coefficients were measured. Hematoxylin-eosin(HE) staining assessed pulmonary histopathology, PAS staining evaluated mucus secretion, Masson’s staining examined collagen fiber deposition levels, ELISA was used to measure inflammatory cytokine levels in serum and bronchoalveolar lavage fluid. Tissue immunofluorescence assessed immune cell levels, while liquid chromatography-mass spectrometry(LC-MS) analyzed small-molecule metabolites to investigate the biological metabolic pathways involving characteristic metabolites.

RESULTS Compared with the model group, mice in the Guanosine-H group showed significantly improved pulmonary tissue pathology, with particularly greater and statistically significant improvements in airway inflammation and alveolar structural repair(P<0.01). Immunocyte analysis revealed that guanosine significantly regulated immune indicators related to eosinophils, Th2 cells, and macrophages in lung tissues, inhibited related inflammatory responses, and suppressed the secretion of related cytokines. Metabolomic analysis revealed that guanosine significantly improved OVA-induced metabolic dysregulation by modulating key pathways including amino acid metabolism and lipid metabolism. Notably, the Guanosine-H group exhibited more pronounced effects in regulating these metabolic pathways(P<0.05).

CONCLUSION In the mouse model of allergic asthma under the experimental conditions, guanosine demonstrated anti-asthmatic effects by regulating immune cell infiltration, improving pulmonary tissue pathology, and modulating key metabolic pathways such as amino acid and lipid metabolism. This study provides experimental theoretical support for guanosine as a novel anti-allergic asthma therapy and lays an experimental foundation for its future clinical application.