Sepsis-induced acute lung injury (ALI) is a severe complication of sepsis. Karanjin, a natural flavonoid compound, has been proved to have anti-inflammatory function, but its role in sepsis-stimulated ALI is uncertain. Herein, the effect of karanjin on sepsis-stimulated ALI was investigated. We built a mouse model of lipopolysaccharide (LPS)-stimulated ALI. The histopathological morphology of lung tissues was scrutinized by hematoxylin-eosin (H&E) staining. The lung injury score and lung wet/dry weight ratio were detected. The myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were scrutinized by commercial kits. Murine alveolar lung epithelial (MLE-12) cells were treated with LPS to mimic a cellular model of ALI. The cell viability was scrutinized by the CCK-8 assay. The contents of proinflammatory cytokines were scrutinized by qRT-PCR and ELISA. The TLR4 and MyD88 contents were scrutinized by qRT-PCR and western blotting. Results showed that karanjin alleviated LPS-stimulated ALI in mice by inhibiting lung tissue lesions, edema, and oxidative stress. Moreover, karanjin inhibited LPS-stimulated inflammation and TLR4 pathway activation in mice. However, treatment with GSK1795091, an agonist of TLR4, attenuated the effects of karanjin on LPS-induced ALI. Furthermore, karanjin repressed LPS-stimulated inflammatory response and TLR4 pathway activation in MLE-12 cells. Overexpression of TLR4 attenuated karanjin effects on LPS-stimulated inflammatory responses in MLE-12 cells. In conclusion, karanjin repressed sepsis-stimulated ALI in mice by suppressing the TLR4 pathway.
Keywords: TLR4; acute lung injury; inflammation; karanjin; sepsis.
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