Wuwei Shaji powder alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via the S-sulfhydration of Keap1
Ethnopharmacological relevance Asthma is a chronic inflammatory airway disease. Current treatments have limited efficacy and often cause severe side effects. Wuwei Shaji Powder (WSP), a traditional Mongolian remedy, is used for treating chronic pulmonary diseases, but its efficacy against asthma and underlying mechanisms are still unclear. Aim of the study To investigate the therapeutic effect of WSP on asthma and elucidate its molecular mechanisms. Materials and methods An ovalbumin (OVA)-induced allergic asthma model was established in rats. Ferroptosis or apoptosis was induced in BEAS-2B cells using Erastin or CdCl 2 . Various techniques including histopathological staining, ELISA, Western blot, flow cytometry, and transmission electron microscopy were employed to assess WSP's effects and mechanisms. Results WSP alleviated OVA-induced allergic asthma in rats without the immunosuppressive side effects observed with dexamethasone. WSP suppressed ferroptosis in bronchial epithelial cells both in vivo and in vitro. It reduced thiol- and sulfonic-based oxidative stress through Keap1 S-sulfhydration, disrupted the Keap1-Nrf2 interaction, and promoted Nrf2 nuclear translocation. Notably, we discovered that CdCl 2 can induce ferroptosis in BEAS-2B cells, and WSP prevented both ferroptosis and apoptosis in these cells. Conclusion WSP alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via S-sulfhydration of Keap1, providing new insights for its clinical application.
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