Luteolin Attenuates Allergic Nasal Inflammation via Inhibition of Interleukin-4 in an Allergic Rhinitis Mouse Model and Peripheral Blood From Human Subjects With Allergic Rhinitis

Abstract

Objectives: Luteolin is the active component of Perilla frutescens, an herb for the treatment of allergy in Asia. In this study, we aimed to investigate the effects and mechanisms of luteolin treatment.Methods: BALB/c mice sensitized with house dust mite (HDM) to induce allergic rhinitis (AR), and treated with dexamethasone or luteolin. In addition, mononuclear cells from peripheral blood (PBMC) of AR patients were co-cultured with dexamethasone or luteolin, and were re-stimulated with HDM.Results: Luteolin-treated mice had decreased allergic symptoms, and serum HDM-specific IgE when compared to the untreated group. Flow cytometric analyses of splenocytes and nasal lymphoid tissues from AR mice found that luteolin decreased CD4+ IL-4-secreting T cells when compared to those from vehicle treated AR mice. Histopathology sections showed reduced infiltration of eosinophils and decreased mucus secretion of mouse nasal epithelium. In the in vitro study, the results showed that luteolin reduced the percentage of CD4+ IL-4-secreting splenocytes expression was through reducing expression of pSTAT6 and GATA3. PBMCs from AR patients pretreated with luteolin could decrease percentage of CD4+ IL-4-secreting cells.Conclusion: Our study identified that luteolin attenuates allergic nasal inflammation via inhibition of IL-4 production, which supports the potential pharmaceutical application of luteolin treatment for AR.

Luteolin as a modulator of skin aging and inflammation

“…Interestingly, luteolin as the active component of Perilla frutescens L. (Lamiaceae) was also shown to inhibit the production of IL‐4 in a house dust mite (HDM) induced murine Balb/c model of allergic rhinitis. This was also seen in mononuclear cells from peripheral blood of allergic rhinitis patients restimulated with HDM 95 . This indicates that not only type IV hypersensitivity reactions or AD but also type 1 reactions can be suppressed by luteolin and that due to the effect of luteolin on IgE and IL‐4 luteolin might also reduce contact urticaria reactions (Figure 3).…”

Mesua ferrea L. (Calophyllaceae) exerts therapeutic effects in allergic asthma by modulating cytokines production in asthmatic rats

“…It also inhibits TLR-4 activation and decreases the production of IL-8, IL-4, IL-5, IL-13, and TNF-α by inhibiting Akt phosphorylation (Gong et al, 2013;Chung et al, 2015). Similarly, alleviations in levels of different cytokines by luteolin treatment in animal as well as in human subjects are also documented (Das and Ghosh, 2003;Liang et al, 2020). Triterpenoid lupeol significantly modulates the level of type II cytokines (IL-4, IL-5 and IL-13) during in vivo experiments (Vasconcelos et al, 2008).…”

Allergic rhinitis, allergic contact dermatitis and disease comorbidity belong to separate entities with distinct composition of T-cell subsets, cytokines, immunoglobulins and autoantibodies

“…On the other hand, IgG could induce an allergic process by activating FcγRs on different cell types when allergen levels are high [ 30 ]. The elevation of serum IgG was also found in the mouse model of AR disease [ 31 ], besides, the nasal IgG was higher in AR patients compared with healthy controls [ 32 ]. There are four subclasses of IgG (IgG1, IgG2, IgG3 and IgG4).…”