Oroxin B prevented sepsis-evoked acute lung injury by promoting M2 macrophage polarization through the TLR4/NF-κB axis.

Acute lung injury (ALI) is a frequent complication of sepsis that aggravates sepsis mortality and morbidity, which is tightly related to the inflammatory process. Oroxin B (OB), a flavonoid from <i>Oroxylum indicum</i> (L.) Vent, has exhibited anti-inflammatory properties in several illnesses. Nevertheless, it is still unclear how OB affects sepsis-induced ALI and how it works. RAW264.7 cells were challenged with lipopolysaccharide (LPS, 10 μg/mL), and mice received cecal ligation and puncture (CLP) to produce sepsis-evoked ALI in <i>in vitro</i> and <i>in vivo</i> models. The action of OB on sepsis-elicited ALI was probed through cell counting kit-8, pathological staining, enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, and western blot. The results showed that OB improved pathological damage and pulmonary fibrosis in CLP-challenged mice. OB also reduced the concentration of MPO, the protein content in BALF, and macrophage and neutrophil numbers in BALF from CLP-challenged mice. Molecularly, OB decreased the levels of IL-1β, IL-6, TNF-α, CD86, and iNOS but increased the level of Arg1 and CD206 in both LPS-evoked RAW264.7 cells and CLP-treated mice. Mechanistically, OB downregulated the level of the TLR4/NF-κB axis in both LPS-challenged RAW264.7 cells and CLP-treated mice. Overexpression of TLR4 abrogated the effect of OB on the above-mentioned indicators in LPS-elicited RAW264.7 cells. Therefore, OB improved sepsis-elicited ALI by attenuating inflammation and promoting M2 macrophage polarization through the TLR4/NF-KB signaling pathway.