The regulatory effects of luteolin, calycosin, and formononetin on the NLRP3/IL-33/ILC2s axis in the treatment of allergic rhinitis: mechanistic analysis and therapeutic potential

木犀草素、芒柄花素和芒柄花素对NLRP3/IL-33/ILC2s轴在过敏性鼻炎治疗中的调节作用:机制分析及治疗潜力

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Abstract

Allergic rhinitis (AR), a common IgE-mediated inflammatory condition of the nasal mucosa, presents with nasal itching, episodic sneezing, and runny nose. Emerging evidence indicates that type 2 innate lymphoid cells (ILC2s) are key players in AR development. Epithelial-derived alarmins (IL-33, IL-25, TSLP) activate ILC2s, leading to Th2 cytokine production (IL-4, IL-5, IL-13) that enhances inflammation. Recent research shows that NOD-like receptor protein 3 (NLRP3) can function as a transcriptional regulator of interleukin-33 (IL-33), offering new mechanistic insights into ILC2s dysregulation. Based on analysis and pharmacological validation of various effective components against AR, three compounds-luteolin, calycosin, and formononetin-have been identified as key ingredients due to their notable anti-inflammatory properties. This review systematically explores how these compounds regulate the NLRP3/IL-33/ILC2s signaling pathway, laying the groundwork for developing targeted AR treatments.

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