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A dihydrofuro[2,3-b] benzofuran derivative alleviates lipopolysaccharide induced acute lung injury via suppressing MAPK signaling

Year: 2026

Type: article

Abstract: Introduction Rhodomyrtus tomentosa (Ait.) Hassk. (Myrtaceae) has been traditionally used in Southeast Asia to treat inflammation, fever, and respiratory ailments. However, its bioactive components and molecular mechanisms remain unclear. To design novel dihydrofuro [2,3-b]benzofuran derivatives inspired by R. tomentosa constituents and to evaluate their anti-inflammatory activity and mechanism in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model. Methods A series of rhodomentosone-like compounds were screened in LPS-stimulated RAW264.7 macrophages for IL-1 β and TNF- α expression. The most active molecule, QFM-3m, was tested in LPS-induced murine ALI through histopathology, cytokine assays, and vascular permeability analysis. Mechanistic studies were conducted using transcriptomic and protein analyses of primary macrophages. Results QFM-3m significantly inhibited LPS-induced IL-1a , IL-1 β , IL-6 and TNF- α expression in vitro and attenuated lung inflammation, cytokine production, and vascular leakage in vivo . Transcriptomic, western blot and molecular docking analysis revealed that QFM-3m selectively suppressed ERK, JNK, and p38 phosphorylation, while NF-κB activation remained unaffected. Conclusion QFM-3m, a novel dihydrofurobenzofuran derivative derived from R. tomentosa , exerts potent anti-inflammatory and lung-protective effects through selective inhibition of the MAPK pathway. These findings highlight the therapeutic potential of R. tomentosa -inspired scaffolds for inflammatory lung diseases.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1763318