Prunetin Protects Against Sepsis‐Induced Acute Lung Injury by Inhibiting Inflammation and Oxidative Stress via Regulating the TLR4 / NF ‐ κB / NLRP 3 Inflammasome Pathway

Prunetin is a naturally occurring flavonoid with effective therapeutic potential against diverse diseases. This study aimed to investigate the potential properties of prunetin in alleviating lipopolysaccharide (LPS)-induced inflammatory responses and oxidative stress in an acute lung injury (ALI) mouse model and murine alveolar macrophages (MH-S cells). The results showed that prunetin protected against LPS-induced ALI in mice, as shown by improved histopathological alterations in lung tissues, reduced lung injury score, and decreased lung wet/dry weight ratio. Furthermore, prunetin attenuated LPS-induced inflammatory responses and oxidative stress both in vivo and in vitro. Prunetin treatment attenuated LPS-induced increase in the expression of toll-like receptor 4 (TLR4), phosphorylated nuclear factor kappa B (NF-κB) p65, nuclear p65, NLR family pyrin domain containing 3 (NLRP3), and ASC, implying that prunetin inhibited LPS-induced activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. Moreover, TLR4 overexpression abolished the inhibitory effects of prunetin on LPS-induced inflammatory responses and oxidative stress in MH-S cells. In summary, our results suggested that prunetin protected against LPS-induced ALI through inhibiting inflammation and oxidative stress via regulating the TLR4/NF-κB/NLRP3 inflammasome pathway. These results support that prunetin may serve as a promising agent for the treatment of sepsis-related ALI.