Platycodon D protects human nasal epithelial cells from pyroptosis through the Nrf2/HO-1/ROS signaling cascade in chronic rhinosinusitis

• DOI: 10.1186/s13020-024-00897-y
• Publication Date: 2024-03-04T04:10:12Z
• Authors: Ruizhi Wang; Yongchun Wang; He Liu; Jinxiang Zhu; Caishan Fang; Weizhen Xu; Zesheng Lu; Yajie Yan; Weiping He; Yan Ruan; Min Zhou
• Keywords: Pyroptosis; Proinflammatory cytokine

Abstract Background Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) emerged as a key anti-inflammatory mediator of various respiratory diseases. This study aims at investigating whether PLD could reduce CRS by inhibiting pyroptosis. Methods Nasal mucosal tissues from patients and control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining expression pyroptosis-related makers immunofluorescence (IF). Human epithelial cells (HNEpCs) cultured co-stimulated lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an vitro cellular model simulating CRS. After pretreatment PLD, EthD-I staining, TUNEL transmission electron microscopy (TEM), GSDMD-NT detection performed evaluate pyroptosis markers. The NLRP3 inflammasome was detected IF western blotting (WB). Reactive oxygen species (ROS) H2DCFDA mitochondrial membrane potential evaluated JC-1 staining. Mitochondrial morphology structure observed TEM. Nrf2/HO-1 antioxidant signaling pathway WB. Results mucosa exhibited significant damage, marked increase proteins compared group. LPS/ATP co-stimulation resulted increased IL-18 IL-1β HNEpCs, causing damage nuclear cell membranes, accumulation around membrane, intracellular activation. Furthermore, it led ROS expression, significantly decreased potential, damaged structure. reversed aforementioned trends activated pathway. Conclusions results this confirm that NLRP3-mediated plays crucial role pathological process impairment inhibits pyroptosis, preventing HNEpCs activating pathway, which turn reduces production ameliorates damage.