Hispidulin Alleviates Mast Cell-Mediated Allergic Airway Inflammation through FceR1 and Nrf2/HO-1 Signaling Pathway

https://www.mdpi.com/2076-3921/13/5/528

Antioxidants / Volume 13 / Issue 5 / 10.3390/antiox13050528 / Published: 26 April 2024

Seungwon Jeong, Yeon-Yong Kim, Dongwon Lee, Sang-Hyun Kim and Soyoung Lee

Abstract

Allergic asthma is a type 2 immune-response-mediated chronic respiratory disease. Mast cell activation influences the pathogenesis and exacerbation of allergic asthma. Therefore, the development of mast cell-targeting pharmacotherapy is important for managing allergic airway inflammation. We investigated the efficacy of hispidulin (HPD), natural flavone, in a mast-cell-mediated ovalbumin (OVA)-induced allergic airway inflammation model. HPD alleviated symptoms of allergic asthma and decreased the levels of immunoglobulin (Ig) E, type 2 inflammation, immune cell infiltration, and mast cell activation in the lung. Furthermore, in vivo analysis confirmed the efficacy of HPD through the evaluation of IgE-mediated allergic responses in a mast cell line. HPD treatment inhibited mast cell degranulation through inhibition of the FcεR1 signaling pathway and suppressed the expression of inflammatory cytokines (TNF-α, IL-4, IL-6, and IL-13) through suppression of the NF-κB signaling pathway. The antioxidant effects of HPD in activated mast cells were identified through modulation of antioxidant enzymes and the Nrf2/HO-1 signaling pathway. In conclusion, HPD may be a potential therapeutic candidate for allergic airway inflammation of asthma and acts by suppressing mast cell activation and oxidative stress.

Keywords: hispidulin; allergic asthma; airway inflammation; mast cell; oxidative stress

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