Abstract
Background: The dried flower buds of Lonicera japonica Thunb. (LJFB) have traditionally been used for febrile- and inflammation-related conditions. Its anti-inflammatory activity provides a rationale for further investigating its protective effects against acute lung injury (ALI), although the underlying chemical and molecular basis remains incompletely understood. Methods: Ultra-Performance Liquid Chromatography–tandem mass spectrometry (UPLC–MS/MS) was employed to profile the chemical constituents of LJFB. Human transcriptomic datasets were analyzed using differential expression analysis and weighted gene co-expression network analysis (WGCNA). These results were integrated with network pharmacology and machine learning to prioritize candidate targets and related signaling pathways. The protective effects of LJFB and associated molecular changes were subsequently assessed in rats with ALI elicited by LPS. Results: A total of 24 constituents were identified, of which 11 were quantified. Integrated network pharmacology and transcriptomic analyses prioritized PI3K–AKT and NF-κB signaling for further investigation, while machine learning prioritized the Pim-1 proto-oncogene, a serine/threonine kinase (PIM1), as a candidate target. In vivo experiments showed that LJFB alleviated pulmonary edema and histopathological injury and improved inflammation- and apoptosis-related abnormalities. LJFB also reduced PIM1 protein expression and decreased the p-PI3K/PI3K, p-AKT/AKT, p-IκBα/IκBα, and p-p65/p65 ratios. Intervention with the PI3K activator 740Y-P partially reversed several protective effects of LJFB and the associated signaling changes. Conclusions: LJFB alleviated ALI triggered by LPS in rats. These findings support the involvement of PI3K–AKT signaling in LJFB-associated protection, accompanied by changes in NF-κB-related signaling. PIM1 was further prioritized as a candidate target for subsequent functional investigation.