Role and mechanism of quercetin via the TLR4/MyD88/IRAK4 signaling pathway in the treatment of allergic rhinitis

Although quercetin has anti-allergic and anti-inflammatory properties, its role in allergic rhinitis (AR) and its potential molecular mechanism, especially whether it acts through the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/interleukin-1 receptor-associated kinase 4 (IRAK4) signaling pathway, is currently unclear. Therefore, an ovalbumin (OVA)-induced AR mouse model was established to investigate whether quercetin can treat AR by regulating the TLR4/MyD88/IRAK4 signaling pathway. OVA and aluminum hydroxide were injected intraperitoneally for sensitization, and OVA was dripped into the nose to establish a mouse model of AR. The mice were scored on behaviors such as scratching, sneezing and a runny nose to assess the success of the modeling. The treatment groups were given the relevant drugs (dexamethasone and quercetin) by gavage for 1 week after successful modeling. Following the completion of treatment, the serum OVA-IgE, IL-4, IL-13, IL-1β, IL-17 and IL-10 levels were measured; changes in the nasal mucosa were observed; protein and mRNA expression levels of TLR4, MyD88, IRAK4 and NF-κB in lung tissue were determined; and changes in the percentages of regulatory T cells (Tregs) and T helper 17 (Th17) cells in the spleen were assessed. The results showed that compared with the normal control (NC) group, the allergic symptom scores were >10 points, and the serum levels of OVA-IgE, IL-4, IL-13, IL-1β and IL-17 increased, whereas the serum level of IL-10 decreased in the OVA group. Detachment and necrosis of the nasal mucosa, accompanied by tissue edema and inflammatory cell infiltration, were observed in the OVA group. Compared with the NC group, the relative expression mRNA and protein levels of TLR4, MyD88, IRAK4 and NF-κB in lung tissues increased, the percentage of Tregs decreased and the percentage of Th17 cells increased in splenocytes of the OVA group. Based on these results, it was hypothesized that quercetin inhibits inflammatory responses and induces immune tolerance by regulating the TLR4/MyD88/IRAK4 signaling pathway in a mouse model of AR.