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.