Bavachinin alleviates allergic rhinitis by modulating gut microbiota and inhibiting NLRP3-mediated epithelial pyroptosis through PI3K/AKT/NF-κB signaling pathway.

Allergic rhinitis (AR), a chronic, non-infectious nasal mucosal inflammation, for which there is no drug that can completely cure it. Bavachinin (BVC), a natural bioactive flavanone from Psoraleae Fructus, has anti-inflammatory and anti-asthmatic properties. However, its effects on AR and the associated mechanism remain unclear. In this study, network pharmacology and molecular docking results showed that AR treatment outcomes using BVC are closely related to the PI3K- Akt pathway and that BVC has a strong binding affinity for NLRP3 and PI3K. BVC showed significant therapeutic effects on AR-model mice, manifesting significant relief of nasal disease signs, suppression of the allergic inflammatory response, a reduction in nasal epithelial pyroptosis, and restoration of the epithelial barrier function. Furthermore, after BVC treatment, the disrupted gut microbiota of AR-model mice showed a tendency to recover, and the intestinal barrier-related protein expression was upregulated. In vitro experiments showed that BVC effectively inhibited the LPS-induced expression of proinflammatory factors. In addition, BVC counteracted the downregulated expression of ZO-1 and Claudin-1. The protective effect of BVC was found to be primarily derived from its inhibitory effect on the PI3K/AKT/NF-κB pathway, thereby suppressing classical NLRP3 inflammasome-mediated pyroptosis. In conclusion, these results indicate that BVC alleviates AR primarily by suppressing NLRP3-mediated pyroptosis via the PI3K/AKT/NF-κB pathway to restore nasal epithelial barrier functions and concomitant restoration of the gut microbiota composition.