Monotropein alleviates sepsis-elicited acute lung injury via the NF-κB pathway

Abstract

Objectives To address the effect and mechanism of Monotropein (Mon) on sepsis-induced acute lung injury (ALI). Methods ALI model was established by lipopolysaccharide (LPS)-stimulated mouse lung epithelial cell lines (MLE-12) and cecal ligation and puncture (CLP)-treated mice, respectively. The function of Mon was examined by cell counting kit-8 (CCK-8), pathological staining, the pulmonary function examination, flow cytometry, enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labellingand western blot. Results Mon increased the LPS-reduced viability but decreased the LPS-evoked apoptosis rate in MLE-12 cells. Mon suppressed the concentrations and protein expressions of proinflammatory factors, and the expressions of fibrosis-related proteins in LPS-challenged MLE-12 cells compared with LPS treatment alone. Mechanically, Mon downregulated the levels of NF-κB pathway, which was confirmed with the application of the receptor activator of nuclear factor-κB ligand (RANKL). Correspondingly, RANKL reversed the ameliorative effect of Mon on the proliferation, apoptosis, inflammation and fibrosis. Moreover, Mon improved the pathological manifestations, apoptosis, the W/D ratio and pulmonary function indicators in CLP-treated mice. Consistently, Mon attenuated inflammation, fibrosis and NF-κB pathway in CLP-treated mice. Conclusion Mon inhibited apoptosis, inflammation and fibrosis to alleviate sepsis-evoked ALI via the NF-κB pathway.

Coptisine attenuates sepsis lung injury by suppressing LPS-induced lung epithelial cell inflammation and apoptosis

“…11,12 Sepsis stimulates the activation of NF-κB, which then enters the nucleus of the cell and initiates the transcription of multiple pro-inflammatory genes, thus promoting inflammation and leading to the development of ALI. 13 In contrast, when NF-κB is downregulated by various methods, such as small interfering RNA (siRNA), shionone (triterpenoid component), topotecan, ghrelin, and monotropein, this inflammatory response is attenuated, [14][15][16][17][18] which results in a reduction of inflammation and lung injury observed in sepsis, potentially contributing to a lower mortality rate. [14][15][16][17][18] Therefore, NF-κB is indeed a critical factor that affects the development and progression of sepsis-induced ALI.…”