Inhibitory functions of cardamonin against particulate matter-induced lung injury through TLR2,4-mTOR-autophagy pathways

Particulate matter with an aerodynamic diameter equal to or less than 2.5 μm (PM_2.5) is a form of air pollutant that causes significant lung damage when inhaled. Cardamonin, a flavone found in Alpinia katsumadai Heyata seeds, has been reported to have anti-inflammatory and anticoagulative activity. The aim of this study was to determine the protective effects of cardamonin on PM_2.5-induced lung injury. Mice were treated with cardamonin via tail-vein injection 30 min after the intratracheal instillation of PM_2.5. The results showed that cardamonin markedly reduced the pathological lung injury, lung wet/dry weight ratio, and hyperpermeability caused by PM_2.5. Cardamonin also significantly inhibited PM_2.5-induced myeloperoxidase (MPO) activity in lung tissue, decreased the levels of PM_2.5-induced inflammatory cytokines and effectively attenuated PM_2.5-induced increases in the number of lymphocytes in the bronchoalveolar lavage fluid (BALF). And, cardamonin increased the phosphorylation of mammalian target of rapamycin (mTOR) and dramatically suppressed the PM_2.5-stimulated expression of toll-like receptor 2 and 4 (TLR 2,4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1. In conclusion, these findings indicate that cardamonin has a critical anti-inflammatory effect due to its ability to regulate both the TLR2,4-MyD88 and mTOR-autophagy pathways and may thus be a potential therapeutic agent against PM_2.5-induced lung injury.