Ginsenoside Rg5 alleviates allergic rhinitis in rats by modulating nasal microbiota by inhibiting JAK2/STAT3/BCL-2 and MAPK signaling

Allergic rhinitis (AR) is a non infectious chronic inflammatory disease of nasal mucosa mediated by IgE and driven by type 2 immune response. Ginsenoside Rg5 (Rg5) is a bioactive compound derived from ginseng, but its effect on AR is unknown. This study investigated the therapeutic potential of Rg5 in toluene diisocyanate (TDI)-induced AR and explored its potential mechanism involving JAK2/SATAT3/BCL-2 and MAPK signaling pathways as well as nasal microbiota regulation AR model was established by TDI sensitization and different doses of Rg5 were administered to assess symptom scores, IgE, His and cytokine levels. Nasal mucosal tissues and lung tissues were analyzed histopathologically for key proteins in the JAK2/STAT3/BCL-2 and MAPK pathways in the nasal mucosa. Nasal microbiota composition was assessed using 16S rRNA sequencing and signaling pathway correlation analysis was performed. Rg5 significantly reduces IgE, His, and pro-inflammatory factors, increases anti-inflammatory factors, mitigates damage to the nasal mucosa and lung tissues, thereby alleviates nasal symptoms. It suppresses the activation of JAK2/STAT3 and MAPK pathways and upregulates BCL-2 expression. It also increases the abundance of Actinobacteria and Acidobacteria , decreases that of Bacteroidetes and Desulfobacteria , and restores the diversity of nasal microbiota. Rg5 ameliorates AR symptoms by enriching beneficial bacteria (e.g., Campylobacterota , Patescibacteria , and Acidobacteriota ), regulating cytokine levels, and synergistically modulating the JAK2/STAT3/BCL-2 and MAPK pathways. Ginsenoside Rg5 acts synergistically through the JAK2/STAT3/BCL-2 and MAPK signaling pathways while restoring nasal microbiota homeostasis and attenuating TDI-induced AR symptoms, highlighting its potential as a novel therapeutic agent for AR. • It proposes that Rg5 inhibits the MAPK and JAK2/STAT3/BCL-2 signalling pathways to treat AR. • It demonstrates that Rg5 can treat dysbiosis of the nasal microbiota in AR rats. • This study first investigates Rg5's role in AR, showing its therapeutic potential.