AS-1 attenuates the inflammatory response by targeting AKT and MAPK in LPS-activated acute lung injury models

We investigated the effects of 3,28-dihydroxyolean-12-ene (AS-1) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in Balb/c mice and attempted to elucidate its underlying mechanism of action.The levels of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and interleukin-1 (IL-1) were measured using an ELISA kit.Furthermore, we analyzed the protein expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the proteins involved in the kinase B/mitogen-activated protein kinase (AKT/MAPK) signaling pathways by Western blot analysis.Additionally, we evaluated AS-1 for toxicity and teratogenicity using the Cell Counting Kit-8 (CCK-8) assay and the zebrafish embryo toxicity assay.The results revealed that AS-1 suppressed the expression of pro-inflammatory cytokines and the phosphorylation of MAPK-related proteins, while enhancing the phosphorylation of AKT-related proteins.Furthermore, AS-1 was found to be non-teratogenic at concentrations below 12.5 M.These findings suggest that AS-1 may alleviate ALI by modulating the AKT/MAPK signaling pathway.