Protective effect of liriodendrin on IgG immune complex-induced acute lung injury via inhibiting SRC/STAT3/MAPK signaling pathway: a network pharmacology research.

ABSTRACT

The primary objectives of this research were to investigate the protective effects of liriodendrin against IgG immune complex (IgG-IC)-induced acute lung injury (ALI) and to elucidate the underlying mechanisms. This study employed a mouse and cell model of IgG-IC-induced acute lung injury. Lung tissue was stained with hematoxylin-eosin to observe pathological alterations and arterial blood gas analysis was tested. Inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α), were measured using ELISA. The mRNA expression of inflammatory cytokines was assessed via RT-qPCR. Molecular docking and enrichment analysis were combined to identify the most potential signaling pathways modulated by liriodendrin, which were then verified using western blot analysis in IgG-IC-induced ALI models. We identified 253 shared targets between liriodendrin and IgG-IC-induced acute lung injury from the database. Through network pharmacology, enrichment analysis, and molecular docking, SRC was determined to be the most closely associated target of liriodendrin in IgG-IC-induced ALI. Pretreatment with liriodendrin notably reduced the increased cytokine secretion of IL-1ß, IL-6, and TNF-α. Histopathological analysis of lung tissue demonstrated a protective effect of liriodendrin on IgG-IC-induced acute lung injury in mice. Arterial blood gas analysis showed liriodendrin ameliorated acidosis and hypoxemia efficiently. Further studies revealed that liriodendrin pretreatment substantially attenuated the elevated phosphorylation levels of SRC's downstream components (JNK, P38, and STAT3), suggesting that liriodendrin may protect against IgG-IC-induced ALI via the SRC/STAT3/MAPK pathway. Our findings indicate that liriodendrin protects against IgG-IC-induced acute lung injury by inhibiting the SRC/STAT3/MAPK signaling pathway, suggesting that liriodendrin may serve as a potential treatment for acute lung injury caused by IgG-IC.