Garlic-derived allyl sulfides attenuate house dust mite-induced allergic airway inflammation associated with reduced PI3K/NF-κB signaling

Background Allergic asthma, characterized by chronic airway inflammation, is often triggered by Dermatophagoides pteronyssinus (Der p). Garlic-derived allyl sulfides, including diallyl trisulfide (DATS), diallyl disulfide (DADS), and S -allyl-L-cysteine (SAC), possess anti-inflammatory properties, yet their effects on allergic asthma remain unclear. This study aimed to investigate the protective effects of these compounds on Der p-induced allergic asthma and to elucidate their underlying mechanisms in vivo and in vitro . Methods BALB/c mice were sensitized and challenged to develop allergic asthma and administered with DATS, DADS, or SAC. Histological phenomena were examined using hematoxylin and eosin (H&E) staining. Bronchoalveolar lavage fluid (BALF) was analyzed for pro-inflammatory (TNF-α, IL-1β, IL-12) and anti-inflammatory (IL-10, TGF-β) cytokines, as well as Th1/Th2 markers (IFN-γ, IL-4, IL-5, and IL-13). Serum immunoglobulins, including IgE, IgG1, and IgG2a subclasses, were quantified. Parallel experiments using A549 alveolar epithelial cells examined PI3K/NF-κB signaling via Western blot analysis. Results Among the tested compounds, SAC showed the strongest effects, significantly reducing inflammatory cell infiltration, restoring Th1/Th2 balance by elevating IFN-γ and reducing IL-4, IL-5, and IL-13, and lowering TNF-α, IL-1β, and TGF-β while enhancing IL-10. SAC also decreased total IgE and IgG1 while increasing IgG2a, suggesting a shift toward Th1-mediated immunity. In A549 cells, SAC inhibited Der p-induced PI3K and IKK expression and suppressed Akt and NF-κB phosphorylation, thereby reducing IL-6 expression. Both in vivo and in vitro findings, complemented by structural molecular visualization, highlight SAC as the most effective for preventing and managing allergic asthma. Conclusion These findings demonstrate that SAC alleviates Der p-induced airway inflammation by modulating immune responses and downregulating PI3K/Akt/NF-κB signaling, highlighting its potential as a natural therapeutic agent for allergic asthma.