Vitamin E exerts a mitigating effect on LPS-induced acute lung injury by regulating macrophage polarization through the AMPK/NRF2/NF-κB pathway

Acute Lung Injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are major threats to human health, characterized by high mortality rates and a lack of effective treatments. Given the significant role of an over-activated inflammatory response and macrophage polarization in the development of ALI, and the unknown effect of vitamin E in this context, our study aimed to explore vitamin E's potential in alleviating ALI. We established an ALI mouse model by intratracheal instillation of LPS and isolated BMDMs for in-vitro experiments. Results indicated that vitamin E treatment significantly reduced LPS-induced lung injury, as shown by decreased lung wet/dry weight ratio, lower levels of pro-inflammatory factors in bronchoalveolar lavage fluid, and improved mouse survival rates. Vitamin E also alleviated oxidative stress by modulating oxidative and reducing products. Mechanistically, it activated the AMPK signal, upregulated NRF2, scavenged Reactive Oxygen Species, inhibited the NF-κB signal pathway, and regulated macrophage polarization towards the anti-inflammatory M2 phenotype while suppressing the pro-inflammatory M1 polarization. In conclusion, vitamin E may serve as a potential Adjuvant treatment for ALI through the AMPK/NRF2 signaling axis, although further research on optimal dosage and combination therapies is needed.

Acute lung injury; Macrophage polarization; Oxidative stress; Vitamin E.