Melastoma dodecandrum polysaccharide alleviates allergic rhinitis in mice through modulating NLRP3 and IL-17 axis

Abstract

Allergic rhinitis (AR) is a prevalent nasal disorder characterized by chronic inflammation and hypersensitivity, with limited effective treatments. Melastoma dodecandrum polysaccharide (MDP), derived from a medicinal herb, exhibits anti-inflammatory and immunomodulatory properties, making it a potential therapeutic candidate for AR. This study evaluated the therapeutic efficacy of MDP in AR mice and explored its underlying mechanisms. An ovalbumin (OVA)-induced AR mouse model was established, with MDP administered via gavage or inhalation. MDP reduced sneezing and nasal scratching in AR mice. Treatment alleviated nasal mucosa thickness, goblet cell hyperplasia, and cellular disarray, as assessed by H&E and Alcian blue staining. MDP decreased serum IgE, IL-17, and IL-1β levels, as measured by ELISA, and reduced the proportion of Th17 cells, analyzed by flow cytometry. In nasal mucosa, MDP downregulated the expression of NLRP3, GSDMD, and IL-17A proteins, and reduced the mRNA levels of NLRP3, IL-17, IL-1β, and IL-18, as determined by immunohistochemistry and qRT-PCR. MDP also mitigated tissue cell death, as shown by TUNEL staining. In vitro, MDP suppressed NLRP3 inflammasome activation and pyroptosis in bone marrow-derived macrophages (BMDMs) treated with LPS and nigericin. These effects were confirmed by western blot, qRT-PCR, and immunofluorescence, along with pyroptosis assessment and scanning electron microscopy, which revealed reduced pyroptosis and membrane damage. In conclusion, MDP effectively alleviates AR symptoms in mice, with its therapeutic effects involving the modulation of the NLRP3 inflammasome and the IL-17 signaling pathway, highlighting its clinical potential for AR management.

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