Background: Macrophages are one of the immune cells involved in the inflammation of acute lung injury(ALI) in the early stage, and the phenotypic changes of macrophages are its important characteristics. Mitochondria plays an important role in the polarization of macrophages. Micheliolide(MCL) is a kind of herbal extract with anti-inflammatory effect, but its specific mechanism is unknown.
Aims: We hypothesized that MCL may reprogram macrophage phenotype by regulating mitochondrial function.

Methods: In vivo,c57BL/6 mice were randomized into control, LPS and MCL+LPS groups. In vitro, We used  MCL to pretreat RAW264.7, then added LPS and IFN-? or same amount of PBS to stimulate the cells. Secretion of pro-inflammatory cytokines, macrophage phenotype, mitochondrial oxidative stress level and mitochondrial respiratory complexes expression and function were examined. Then, we analyzed database to search the protential molecular mechanism for MCL to play a role in ALI.

Results: In vivo, H&E staining result showed that compared with LPS group, MCL pretreatment group had less pulmonary interstitial exudation. Western blot result showed that MCL pretreatment make pro-inflammatory cytokines such as IL-1, IL-6 decreased. In vitro, macrophage M1 polarization and secretion of IL-1, IL-6 reduced after MCL pretreatment. At the same time, MCL alleviated the change of mitochondrial membrane potential caused by LPS and ATP production increased after MCL pretreatment. Comparing with NAC, an antioxidant, SOD activity was restored and MDA level was reduced after MCL treatment as same as NAC pretreatment.