Luteolin attenuate paraquat-induced acute lung injury by regulating autophagy through the PI3K/AKT/mTOR pathway

Acute lung injury (ALI) is the primary cause of death in patients who are affected by paraquat (PQ) poisoning. Luteolin (Lut) is a flavone compound present in several medicinal plants. The present study aimed to explore the protective role of Lut in PQ-induced ALI and the underlying molecular mechanisms. Network pharmacology analysis was used to predict key genes and signaling pathways that were potentially involved in the therapeutic effect of Lut. In vivo , Lut inhibited PQ-induced lung pathological injury and decreased pulmonary vascular endothelial permeability. In vitro , human pulmonary microvascular endothelial cells were pretreated with Lut and then treated with PQ for 72 h. Lut reduced oxidative stress and decreased the production of inflammatory factors including IL-6, TNF-α, and IL-1β. Lut up-regulated the levels of the autophagy-associated proteins LC3-II/I and down-regulated the levels of P62, resulting in an increased number of autophagosomes. However, pretreatment with the autophagy inhibitor 3-methyladenine reversed the effects of Lut on inflammatory responses, oxidative stress, and cellular apoptosis, and the protective effects of Lut were related to regulation of the PI3K/Akt/mTOR pathway. In summary, Lut enhanced autophagy by regulating the PI3K/Akt/mTOR pathway, thereby alleviating inflammation and oxidative stress during PQ-induced ALI.