Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Sepsis-associated acute respiratory distress syndrome (ARDS) is a severe inflammatory lung disorder with high mortality. Bruceine A (BA), a quassinoid from Brucea javanica, exhibits anti-inflammatory and immunomodulatory activities, but its role in ARDS is unclear. Objectives: This study evaluated the protective effects of BA in lipopolysaccharide (LPS)-induced ARDS and explored its underlying mechanisms. Methods: Thirty-six C57BL/6 mice were randomized into four groups: control, LPS, LPS+BA and LPS+dexamethasone (Dex). Lung injury was assessed by histopathology, wet/dry weight ratio and TUNEL assay. Cytokine levels (TNF-?, IL-6, IL-1?, IL-10) were measured by ELISA. Macrophage polarization markers (iNOS, COX-2, Arg-1, YM1, CD206) and NF-?B pathway proteins were evaluated using immunohistochemistry and Western blotting. Results: BA significantly alleviated LPS-induced lung injury, reducing edema, tissue damage and alveolar apoptosis. It suppressed proinflammatory cytokines while enhancing IL-10. BA shifted macrophage polarization from proinflammatory M1 toward anti-inflammatory M2 phenotypes. Furthermore, BA inhibited NF-?B activation, evidenced by reduced phosphorylated p65 and restored I?B? levels. These effects were comparable to Dex. Conclusion: BA protects against LPS-induced ARDS in mice by modulating cytokine release, promoting M2 macrophage polarization and suppressing NF-?B activation. These findings suggest BA as a promising natural immunomodulatory agent for inflammatory lung diseases.