Acute lung injury (ALI) is a common disease with complex pathogenesis. However, the treatment is mainly symptomatic with limited clinical options. Asiaticoside (AS), a Chinese herbal extract, has protective effects against LPS-induced ALI in mice and inhibits nitric oxide and prostaglandin E2 synthesis; however, the specific mechanism of AS in the prevention and treatment of LPS-induced ALI needs further study. Sema4D/CD72 pathway, mitochondrial dysfunction, and miRNA-21 are closely associated with inflammation. Therefore, the present study aimed to explore whether AS exerts its therapeutic effect on ALI by influencing Sema4D/CD72 pathway and mitochondrial dysfunction, restoring the balance of inflammatory factors, and influencing miRNA-21 expression. Cell and animal experiments were performed to investigate the effect of AS on ALI. Lipopolysaccharide (LPS) was used to establish the ALI model. CCK8 and flow cytometry were used to detect the cell viability and apoptosis rate. HE staining and wet-to-dry weight ratio (W/D) of lung tissue were determined. The expressions of Sema4D, CD72, NF-κB p65, Bax, Bcl2, and caspase 3 in RAW264.7 cells and lung tissues were detected by western blot, and the levels of IL-10 and IL-1β induced by LPS in supernatant of RAW264.7 cells and BALF were measured by ELISA. And the expression of miRNA-21 in cells and lung tissues was detected by fluorescence quantitative PCR. The result shows that AS treatment suppressed LPS-induced cell damage and lung injury in mice. AS treatment could alleviate the pathological changes such as inflammatory infiltration and histopathological changes in the lungs caused by LPS, and reduce the ratio of W/D. AS significantly alleviated the decrease of mitochondrial membrane potential induced by LPS, inhibited the increase of ROS production, and reduced the expression of mitochondrial fission proteins Drp1 and Fis1. The high-dose AS group significantly downregulated the expression of Sema4D, CD72, phosphorylated NF-κB p65, and apoptosis-related proteins, decreased the pro-inflammatory factor IL-1β, and enhanced the level of anti-inflammatory factor IL-10. In addition, AS promoted miRNA-21 expression. These effects inhibited apoptosis and restored the balance between anti- and pro-inflammatory factors. This represents the inaugural report elucidating the mechanism by which AS inhibits the Sema4D/CD72 signaling pathway. These findings offer novel insights into the potential application of AS in both preventing and treating ALI.
Keywords: Asiaticoside; Lipopolysaccharide-induced acute lung injury; MicroRNA-21; Mitochondrial dysfunction; Sema4D.
© 2024. The Author(s).