Investigating the Potential Pharmacological Mechanisms of Huangqi in Allergic Rhinitis Using Network Pharmacology and Molecular Docking Strategies.

Abstract

Background: Allergic rhinitis (AR) is a common immune disorder that substantially impairs quality of life. Huangqi, a traditional Chinese medicine (TCM), exhibits notable antiinflammatory and anti-allergic effects. However, the molecular mechanisms underlying its therapeutic effects on AR remain unclear. This study aimed to systematically elucidate the targets and pharmacological mechanisms of Huangqi in the treatment of AR.

Methods: We utilized network pharmacology, molecular docking, and Mendelian randomization analysis to identify candidate genes associated with AR. An AR cell model was established using house dust mite (HDM) stimulation to explore the expression and regulatory roles of these genes in vitro. Additionally, an HDM-induced AR mouse model was developed to validate the therapeutic mechanisms of Huangqi in vivo.

Results: Network pharmacology identified 168 target genes associated with Huangqi in relation to AR, among which 32 core genes were selected based on degree, closeness, and betweenness centrality metrics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that oxidative stress, transcriptional regulation, and inflammatory pathways are the primary mechanisms involved. Molecular docking results revealed that kaempferol exhibited the highest binding affinity to SRC (-11.9 kcal/mol). Mendelian randomization analysis further established a potential causal relationship between TNF, SRC, BCL2, and AR. Both in vitro and in vivo experiments confirmed that kaempferol significantly inhibited inflammation-related gene expression by downregulating SRC.

Discussion: These findings suggest that Huangqi, through its active compound kaempferol, mitigates AR by modulating inflammatory pathways, with SRC serving as a pivotal molecular target, providing new insights for the development of clinical interventions.

Conclusions: Kaempferol is likely the key active component of Huangqi in the treatment of AR, primarily exerting its therapeutic effects through the modulation of SRC expression.