Systematic transcriptome and molecular docking analyses reveals that Cirsium japonicum mitigates allergic nasal inflammation through regulation of NRF2-mediated mucin production in an allergic rhinitis mouse model
Allergic rhinitis (AR) is a typical allergic disease mediated by immunoglobulin E (IgE), which greatly affects the quality of life and is more sensitive to change of seasons due to various nasal symptoms. AR worsening symptoms can lead to more dangerous diseases, there is an urgent need to develop safe and effective treatments. Cirsium japonicum (CSJ) is a plant that has been used in traditional medicine due to its various efficacy and safety; so far, the effects and major mechanisms of CSJ on AR have not been reported. Therefore, the purpose of this study was to investigate the possible targets of CSJ for AR treatment and its underlying mechanisms. An ovalbumin (OVA)-induced AR mouse model was established and the therapeutic effects of CSJ were evaluated. CSJ reduced the production level of OVA-specific IgE, histamine, and Th2 cytokines in serum, and significantly alleviated the typical symptoms of AR and the level of inflammation in the nasal mucosa. In addition, we used transcriptome analysis in AR models to identify that O-linked glycosylation of mucins, MUC5AC, and NRF2 are key targets for CSJ related to AR. Then, we identified the active ingredients of CSJ for AR, and verified that the active core compounds of CSJ, cryptochromogenic acid and cirsimarin, could bind closely to potential key targets, NRF2-KEAP1, and MUC5AC using molecular docking analysis. In conclusion, our results suggest that CSJ may be a more effective candidate drug for the treatment of AR with dual function to regulate both NRF2 pathway and MUC5AC expression. Overall design: To investigate the gene expression signatures of Cirsium japonicum (CSJ), we performed whole transcriptome sequencing (WTS) in an OVA-induced AR mouse model treated with two increasing doses of CSJ.