Potential of Ginger Oil to Prevent 4‐(Methylnitrosamino)‐1‐(3‐Pyridyl)‐1‐Butanone‐Induced Lung Cancer Through Gut Microbiota Modulation and Inflammatory Response Inhibition

Lung cancer remains the leading cause of cancer-related mortality worldwide, with tobacco carcinogens such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) playing a central role in its pathogenesis. Chemoprevention through dietary or natural compounds offers a promising strategy to mitigate cancer risk. Published studies have indicated that ginger oil (GIO), a bioactive extract from ginger, possesses various bioactivities, suggesting its potential for cancer chemopreventive. In this study, we aimed to investigate the lung cancer chemopreventive potential of GIO. An NNK-induced lung cancer model in A/J mice was utilized to evaluate the preventive effect of GIO against lung cancer. Additionally, the potential mechanisms by which GIO might prevent NNK-induced lung cancer were assessed using molecular biology techniques combined with multi-omics. The results demonstrated that GIO decreased the number of lung tumors in the lungs of mice. Mechanistically, GIO exerts chemopreventive effects by modulating both the TLR4/NF-κB and PPARγ/NF-κB signaling axes, thereby suppressing downstream pro-inflammatory mediators. Furthermore, GIO modulates gut microbiota composition and its metabolites. Critically, its lung chemopreventive efficacy against NNK-induced lung carcinogenesis is partially dependent on microbiota-mediated regulation. Overall, these findings underscore the nutritional value of GIO as a diet-derived chemopreventive agent against lung cancer caused by tobacco carcinogens.