Luteolin alleviates neurogenic inflammation in OVA-induced combined allergic rhinitis and asthma syndrome mice through TRPV1/ERK-related signaling

OBJECTIVE: Combined Allergic Rhinitis and Asthma Syndrome (CARAS), a common chronic allergic respiratory disease, involves dysregulated neuro-immune interactions and neurogenic inflammation. Luteolin (LUT) has significant anti-inflammatory and antioxidant activities. However, its effects and underlying mechanism in CARAS remain unclear. This study aims to determine the effects of LUT administration during the airway challenge phase of CARAS and its association with TRPV1/ERK signaling. METHODS: BALB/C mice were used to establish an ovalbumin (OVA)-induced CARAS model and LUT was administered. The nasal symptoms were evaluated by counting the number of nasal scratching and sneezing. HE and toluidine blue staining were performed to determine the histopathological changes. Total and differential cell counts in bronchoalveolar lavage fluid (BALF) were determined. The levels of histamine, MCP-1, substance P (SP), CGRP and Th1/Th2/Th17-related cytokines were detected by ELISA kit. Besides, TRPV1 and p-ERK expression levels were measured by immunofluorescence staining and Western blotting. RESULTS: Our study indicated that LUT administration significantly reduced sneezing frequency, nasal scratching behavior, and serum OVA-specific IgE level in CARAS mice compared to the model group. Histopathological analysis demonstrated that LUT administration reduced inflammatory cell accumulation and histological scores in the nasal mucosa and lung tissues and was associated with reduced inflammatory cell counts in BALF. In addition, LUT administration reduced mast cell density in both tissues. Serum histamine and MCP-1 levels and pulmonary levels of IL-4, IL-5, IL-13, IL-17A, and IFN-γ were also reduced following LUT administration. LUT administration also reduced serum and BALF levels of SP and CGRP. Furthermore, LUT administration reduced TRPV1 expression and p-ERK levels in the nasal mucosa and lung tissue. CONCLUSION: LUT administration attenuates allergic and inflammatory responses in OVA-induced CARAS mice, which may be associated with TRPV1/ERK signaling.