7-Methoxyflavanone Alleviates LPS-Induced Acute Lung Injury by Suppressing TLR4/NF-κB p65 and ROS/Txnip/NLRP3 Signaling

Background: Acute lung injury (ALI) is a serious respiratory condition. The natural compound 7-Methoxyflavanone (7MF) has a broad spectrum of anti-inflammatory and antioxidant properties. However, its pharmacological effects and underlying mechanisms in alleviating ALI remain poorly understood. Methods: An in vitro LPS-induced RAW264.7 macrophage inflammatory injury assay and an in vivo lipopolysaccharide (LPS)-induced ALI assay in mice were conducted. Results: In vitro experiments showed that 7MF significantly reduced levels of IL1β, IL6, and TNF-α; decreased the expression of COX2 and iNOS, as well as TLR4 and MyD88; suppressed the phosphorylation and degradation of IκBα; and blocked the entry of NF-κB p65 into the nucleus, thereby inhibiting NF-κB signaling. Meanwhile, 7MF also decreased ROS levels; prevented the dissociation of Txnip from Trx-1; and suppressed NLRP3, Caspase-1, Cleaved Caspase-1 p10, NEK7, Caspase-8, Cleaved Caspase-8, IL18, GSDMD, and GSDMD N-terminal expression, and thus inhibited NLRP3 signaling. MCC950, a specific inhibitor of NLRP3, significantly enhanced the pharmacological inhibition of NLRP3 by 7MF. Notably, similar results were confirmed in LPS-induced ALI experiments in mice. Conclusions: The compound 7MF effectively alleviated LPS-induced ALI by suppressing TLR4/NF-κB p65 and ROS/Txnip/NLRP3 signaling pathways. Our findings provide scientific evidence for drug development and treatment of ALI.