Activity and Mechanism of Naringin in the Treatment of Post-Infectious Cough

Objective : To explore activity and mechanism of naringin in the treatment of post-infectious cough by virtue of network pharmacology and animal studies. Methods : The targets associated with naringin were obtained from the Swiss Target Prediction and Super-PRED databases. Disease-related targets were collected from GeneCards, Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD). Venny was utilized to identify the overlapping targets between naringin and the disease. Protein-protein interaction (PPI) networks for disease-related targets were constructed using STRING and Cytoscape 3.10.1. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with Metascape. Molecular docking between key targets and naringin was conducted using AutoDock. In the animal experiments, PIC models were established in guinea pigs via intranasal inoculation with A/PR/8 virus, and cough frequency was measured after citric acid-induced coughing. Morphological changes in lung tissue and airways were assessed using the hematoxylin-eosin (HE) staining method. The relative expression levels of IL-8, IL-1β, TNF-α, and NF-κB mRNA were analyzed by RT-qPCR. Superoxide dismutase (SOD) activity in lung tissue was measured using a colorimetric assay. Results : After screening, naringin may contribute to the treatment of post-infectious cough by targeting proteins expressed by core genes such as HSP90AA1 (HSP 90-alpha), TLR4 (Toll-like receptor 4), MTOR (Mechanistic Target of Rapamycin), HIF1A (Hypoxia-inducible factor alpha), and NF-κB1 (nuclear factor kappa-B subunit 1). KEGG enrichment analysis revealed involvement in pathways including the HIF-1 signaling pathway and the PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking results indicated that naringin exhibited strong binding affinity with HSP90AA1, TLR4, MTOR, HIF1A, NF-κB1, NOS3, and GRB2. In animal experiments, compared to the normal group, guinea pigs in the model group exhibited a significantly higher number of coughs, pronounced lung tissue hyperplasia, and inflammatory cell infiltration. Additionally, the relative expression of IL-8, IL-1β, TNF-α, and NF-κB p65 mRNA was significantly increased, while lung tissue SOD activity was decreased. Treatment with naringin significantly reduced the number of coughs, attenuated pathological changes in lung tissue, lowered the lung index, decreased the relative expression of IL-8, IL-1β, TNF-α, and NF-κB p65 mRNA, and significantly increased SOD activity in lung tissue compared to the model group. Conclusion : Naringin can effectively treat post-infectious cough through anti-inflammatory and antioxidant.