Lonicera caerulea var. edulis in acute lung injury therapy: integrated chemical composition, anti-inflammation, antioxidation, and NF-κB cascades based on bioactivity-guided fractionation

Ethnopharmacological relevance: Lonicera caerulea var. edulis is an Oroqen medicine with fever relief, detoxification, and anti-inflammatory activities. However, pharmacological and chemical research on its leaves is limited. Aim of the study: Focusing on L. caerulea var. edulis leaves, the research involved identification of active constituents, examination of anti-inflammatory effects in mice, and analysis of mechanisms. Materials and methods: Based on activity-guided fractionation, the phytochemicals were separated via various chromatographic and spectroscopic techniques. The anti-inflammatory effects were evaluated in mice with LPS-stimulated acute lung injury. Antioxidant capacity was determined through DPPH^• and OH^• scavenging, ferric-reducing and lipid peroxidation assay. The active compounds were screened in LPS-treated RAW 264.7 macrophage cells. Then, the anti-inflammatory mechanisms were investigated via RT-qPCR, Western blot analysis, and molecular docking experiments. Results: The EtOAc fraction (EF) displayed the strongest anti-inflammatory activity, with a pronounced inhibitory effect on cellular NO production, markedly decreasing the levels of inflammatory factors, effectively improving acute lung injury, and alleviating pulmonary edema in mice. Meanwhile, EF was also the strongest antioxidant layer which could effectively scavenge free radicals. Phytochemical investigation of EF resulted in the isolation of one new diterpenoid and 19 known constituents, of which ten compounds are lignans. Among them, a lignan (8) significantly reduced NO production, inhibited the IL-1β, IL-6, iNOS, and COX-2 gene expression, and decreased the phosphorylation levels of p65 and IκBα in RAW 264.7 macrophages. Additionally, 8 could tightly interact with the p65 and IκBα proteins of NF-κB. Conclusion: The leaves of L. caerulea var. edulis have significant anti-inflammatory properties, and lignans are the main active components, whose anti-inflammatory mechanisms are mainly through inhibiting the NF-κB signaling pathway.