Peimisine ameliorates allergic asthma by suppressing Th2-associated inflammation and oxidative stress

Fritillaria thunbergii Miq. has been traditionally used to treat respiratory disorders in Chinese medicine. Peimisine, a major F. thunbergii alkaloid, has anti-inflammatory and antioxidant effects, but its role in allergic asthma and mucus-driven airway remodeling remains unclear. This study investigated whether peimisine could attenuate asthmatic phenotypes and explored its mechanistic links to Th2 inflammation, epithelial activation, and oxidative stress. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) and treated with peimisine. Airway hyperresponsiveness (AHR) and lung function were measured, and lung tissues were evaluated for inflammatory infiltration, goblet cell hyperplasia/mucus hypersecretion, and remodeling. Inflammatory mediators and oxidative stress indices were determined in bronchoalveolar lavage fluid (BALF) and lung homogenates. In vitro, BEAS-2B bronchial epithelial cells were used to assess inflammatory activation, intracellular reactive oxygen species (ROS) generation, and monocyte-epithelial adhesion. Peimisine significantly improved AHR and reduced airway inflammatory cell infiltration. It also suppressed goblet cell expansion, mucus hypersecretion, and collagen deposition. Mechanistically, peimisine attenuated Th2-skewed inflammation, reducing BALF eosinophils, Th2 cytokines, eotaxins, and OVA-specific IgE/IgG1 while increasing Th1-associated markers and OVA-specific IgG2a. Peimisine restored redox balance and inhibited NF-κB activation in lung tissue. Consistently, peimisine downregulated epithelial eotaxins, ICAM-1, and pro-inflammatory cytokines in BEAS-2B cells, concomitant with reduced ROS production and diminished monocyte adhesion. Overall, peimisine alleviated allergic asthma by reducing airway inflammation and oxidative stress and by limiting Th2 immune activation, thereby decreasing epithelial inflammatory responses, mucus hypersecretion, and airway remodeling. These results suggest that peimisine may be a promising therapeutic candidate for allergic asthma.