Tabersonine inhibits inflammation and apoptosis through the JAK1/STAT3 signaling pathway to alleviate LPS-induced acute lung injury

Tabersonine (Tab) holds potential therapeutic value for acute lung injury (ALI), but its mechanism remains unraveled. In order to delve into the mechanism of Tab in ALI treatment, our research group initially conducted a network pharmacology prediction. The GSE225664 single-cell transcriptome data set concerning ALI was downloaded from the GEO database. Differential expression analysis combined with weighted gene co-expression network analysis were carried out for identifying ALI-related genes. The drug-related database was employed for the prediction of Tab targets. 28 ALI-Tab targets were predicted through network pharmacology. Core target identification, KEGG pathway enrichment analysis, and molecular docking revealed that Janus kinase 1 (JAK1) is the potential target and the JAK-signal transducer and activator of transcription (STAT) signaling pathway is the potential target pathway for Tab in the treatment of ALI. An ALI mouse model, along with a RAW264.7 cell model, was established through lipopolysaccharide (LPS) stimulation, with Tab administered as an intervention. Cells were pretreated with the JAK1 inhibitor. Lung tissue injury and inflammation was evaluated based on six parameters: (1) lung tissue histopathological features, (2) lung wet/dry ratio, (3) inflammatory cell count in bronchoalveolar lavage fluid, (4) total protein concentration, (5) lactate dehydrogenase, and (6) proinflammatory factors. Cell activity was assessed through cell counting kit-8 assay. TdT-mediated dUTP nick-end labeling staining, Western blot, and flow cytometry were adopted to detect apoptosis. Tab pretreatment was proven to be effective in alleviating inflammation in mice with LPS-induced ALI and LPS-stimulated RAW264.7 cells, and suppressing the JAK1/STAT3 signaling pathway activation. Co-culturing LPS-stimulated RAW264.7 cells with A549 cells led to significantly reduced A549 cell apoptosis. Further research demonstrated that the overexpression of JAK1 significantly inhibit the effects of Tab. The foregoing results prove that LPS-induced ALI is attenuated by Tab treatment, with the underlying mechanism believed to involve the JAK1/STAT3 pathway-mediated inflammation and apoptosis.