Acute lung injury (ALI) is a life-threatening disorder featured by pulmonary inflammation, with no highly effective pharmacological treatments available. Given the anti-inflammatory property of garlic (Allium sativum L.) and the therapeutic potential of plant-derived nanovesicles, we hypothesized garlic-derived exosome-like nanovesicles (GAELNs) protect against ALI. In our present study, GAELNs were successfully isolated, purified, and characterized, showing typical exosomal traits and diverse biomolecules. In vivo, GAELNs administration mitigated LPS-induced lung histopathological damage and suppressed pro-inflammatory cytokine production. In vitro, GAELNs were efficiently internalized by RAW264.7 macrophages, leading to reduced secretion of harmful cytokines. Transcriptomic profiling indicated that the anti-ALI effects of GAELNs were associated with modulation of multiple inflammatory signaling pathways. Mechanistically, GAELNs conferred protection by potently inhibiting the cGAS-STING signaling axis and its downstream effectors. Collectively, GAELNs alleviate ALI by inhibiting the cGAS-STING mediated inflammatory cascade, representing a promising novel therapeutic strategy for ALI.

Smoking remains strongly associated with lung cancer, underscoring the need for effective chemopreventive strategies derived from dietary sources. This study is focused on the protective effects of diallyl trisulfide (DATS) against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) triggers lung tumor formation. DATS is a bioactive organosulfur compound sourced from garlic. In an A/J mouse model, DATS administration significantly reduced lung tumor multiplicity. In vitro assays using MRC-5 human lung fibroblasts demonstrated that DATS mitigated NNK-induced cytotoxicity. Mechanistic studies indicated that DATS-mediated Nrf2 pathway activation, via Keap1 dissociation and nuclear translocation, upregulates antioxidant defense genes. Critically, pharmacological inhibition of Nrf2 abolished the protective effects of DATS, pointing to the pathway as central to the effect. Our results position DATS as a promising candidate for dietary prevention of lung cancer. Taken together, this study suggests that DATS has promise as a dietary strategy to prevent lung cancer.