# Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling

## TL;DR

Atractylenolide I reduces allergic responses in mice by blocking a key inflammation pathway, suggesting it could be a new treatment for allergic rhinitis.

## Contribution

This study reveals that Atractylenolide I alleviates allergic rhinitis by suppressing the TLR4/NF-κB/NLRP3 signaling pathway in mice.

## Key findings

- Atractylenolide I reduced sneezing, rubbing, and IgE levels in allergic mice.
- The compound improved Th1/Th2 cytokine imbalance and reduced nasal mucosal inflammation.
- TLR4/NF-κB and NLRP3 pathway activation was inhibited by Atractylenolide I.

## Abstract

Allergic rhinitis (AR) is a frequent respiratory condition characterized by elevated immunoglobulin E (IgE) levels and nasal mucosal inflammation. Atractylenolide I (ATL-I), a bioactive ingredient in medicinal plants, is known for its ability to alleviate tissue damage by inhibiting inflammatory and oxidative stress responses. In this study, we aimed to investigate the protective roles of ATL-I in AR and reveal the potential mechanism involved. The AR model was developed in mice by intraperitoneal sensitization followed by intranasal exposure to ovalbumin. The effects of ATL-I on allergic responses were evaluated by recording sneezing and rubbing frequencies and measuring the serum concentrations of Th1 and Th2 cytokines following the intragastric administration of ATL-I. The activation of the Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) pathway and the NOD-like receptor 3 (NLRP3) inflammasome was assessed via Western blotting and immunohistochemistry. The results showed that ATL-I administration alleviated allergic responses in AR mice, as evidenced by significant decreases in the frequencies of sneezing and rubbing and in the serum concentrations of histamine and IgE. Compared with control mice, AR mice presented downregulated Th1 cytokines and upregulated Th2 cytokines, whereas the Th1/Th2 imbalance was improved by ATL-I. ATL-I reduced the mucosal layer thickness and alleviated goblet cell hyperplasia in AR mice. Furthermore, ATL-I inhibited TLR4/NF-κB pathway activation in mucosal tissues, which resulted in the inactivation of the downstream NLRP3 inflammasome. In summary, our results indicate that ATL-I alleviates allergic responses by inhibiting the TLR4/NF-κB/NLRP3 pathway, providing a promising therapeutic strategy for AR.