Ginsenoside Rg1 attenuates asthma features in mice co-exposed to house dust mite allergen and diesel exhaust particle by modulating epithelial ILC2 interactions.

Background: Airway epithelial cells initiate asthma-related inflammation, making them key therapeutic targets. While some ginsenosides, the principal active constituents of Methods: BALB/c mice were exposed intranasally to Dp and DEP with or without ginsenoside Rg1 treatment. AHR, inflammatory cell counts in bronchoalveolar lavage fluid, serum IgG1 levels, lung histopathology, and cytokine levels were assessed. Lung Th2/Th17 cells and ILC2/ILC3 populations were analyzed by flow cytometry. Mechanistic studies were conducted using MLE-12 lung epithelial cells and ILC2 co-cultures. Results: Co-exposure to Dp and DEP significantly increased AHR, eosinophilic inflammation, Th2/Th17 responses, and ILC2/ILC3 populations. Ginsenoside Rg1 treatment markedly attenuated AHR, reduced eosinophils and serum Dp-specific IgG1, and decreased frequencies of IL-13+ ILC2s and IL-17+ ILC3s. IL-33 and IL-1β levels in lung tissue were also significantly reduced by Rg1. In MLE-12 cells, Rg1 suppressed IL-33 and phosphorylated STAT6 expression, mirroring the effects of a STAT6 inhibitor. Furthermore, Rg1 reduced IL-13 and IL-5 secretion from ILC2s co-cultured with MLE-12 cells. Conclusion: Ginsenoside Rg1 mitigates Dp/DEP-induced airway inflammation by downregulating Th2/Th17 and ILC2/ILC3 responses, potentially via the IL-33-STAT6 axis in airway epithelial cells.