Obtusifolin mitigates acute lung injury and improves cardio-pulmonary functions in acute lung injury model by modulating oxidative stress and NF-κB signaling.

Pulmonary-cardiac inflammation is a serious health condition affecting all age groups caused by either injury or infection. Acute or chronic lung/cardiac disorders cause several disturbances in their functions and architecture, leading to fatality by causing multi-organ failure. Obtusifolin (OBT) is a traditional phytomolecule known for its anti-inflammatory effects in arthritis models. This study aims to investigate the therapeutic effects of OBT against lipopolysaccharide (LPS)-induced lung and cardiac inflammation/injury using both in vitro and in vivo models. In vitro experiments were conducted using RAW 264.7 and THP-1 cells, and in vivo experiments were conducted using an LPS-challenged rat model. Further molecular docking was performed for binding studies. In vitro experiments demonstrated that LPS markedly increased the expression of Tnf-α, Il-6, Ccl-2, Cox-2, and oxidative stress markers, while OBT treatment dose-dependently attenuated these effects. In vivo, intra-tracheal LPS administration elevated inflammatory cell counts/marker expression, accompanied by histopathological changes such as alveolar wall thickening, myocardial degeneration, and inflammatory cell infiltration in lung and cardiac tissues. OBT treatment effectively reversed these alterations, restoring tissue architecture and functional parameters. Furthermore, lung and cardiac functional assessments indicated significant improvements in lung function and ECG parameters. Mechanistically, OBT inhibited LPS-induced caveolin-1 and MIF expression via NF-κB signaling modulation. Molecular docking analysis revealed that OBT binds to the MIF protein with a binding affinity of - 5.952 kcal/mol. Overall, our findings highlight the therapeutic potential of OBT in mitigating lung injury and oxidative stress, paving the way for translational applications.