Luteolin ameliorated CHC-induced autophagy dysfunction in macrophages through the AMPK/mTOR signaling pathway

Abstract Background Macrophages play a crucial role in the progression of atherosclerosis (AS), and cholesterol crystals (CHC) abundantly present in AS can affect the function of macrophages. Studies have found that the flavonoid luteolin (Lut) in nature has multiple functions such as anti-tumor and anti-inflammatory. Objective This experiment intends to explore whether Lut can reverse the autophagy dysfunction of macrophages induced by CHC and whether it can reduce the apoptosis of macrophages caused by CHC, and study its mechanism. Methods The RAW264.7 macrophages were modeled with CHC, and the optimal concentration of Lut was used to act on the inflammatory modeled macrophages. The changes in autophagy protein, apoptosis protein, and apoptosis were observed to confirm whether Lut is effective in the inflammation model. Effects of Lut combined with 3-MA autophagy inhibitor on autophagy and apoptosis of macrophages. Finally, the effect of Lut on the autophagy pathway AMPK and mTOR in inflammation modeling with CHC was studied. Results The expression of LC3-II/LC3-I decreased, p62 increased, and the apoptosis rate increased and the expression of Bax protein, cleaved caspase-3/procaspase-3 increased, tumor necrosis factor TNF- α expression increased. After Lut intervenes in macrophages after CHC action, the above effects are opposite. After CHC acted on macrophages, the phosphorylation of AMPK was significantly inhibited, while the phosphorylation of mTOR was significantly enhanced. After Lut intervention, the above results were the opposite. Conclusion CHC can inhibit the autophagy function of RAW264.7 macrophages and cause macrophage apoptosis. Lut can improve the autophagy dysfunction of macrophages caused by CHC and reduce the apoptosis caused by the inhibition of macrophage autophagy. Lut can regulate the apoptosis of macrophages caused by CHC through the AMPK/mTOR signaling pathway.