Poncirin Protects Against LPS-induced Acute Lung Injury: Targeting MAPKs/NF-kB Signaling Using <i>In vivo</i> , Molecular Docking, MD Simulation and MM-PBSA/GBSA Studies

This study investigated the protective effects of Poncirin, a natural compound isolated from Poncirus trifoliata, against Lipopolysaccharide (LPS)-induced Acute Lung Injury (ALI) in mice using in vivo and computational studies. Lipopolysaccharide was administered Intraperitoneally (IP) at a dose of 10 mg/kg 30 min prior to treatment with Poncirin at doses of 30 mg/kg IP. The temperature of the body was monitored through a thermometer via Intrarectal Route (IR) every 6 h for 24 h, and mortality was recorded throughout the study. The results showed a marked reduction in the body temperature following Poncirin administration, in contrast to the Lipopolysaccharide-induced group. Similarly, the Poncirin administration also reduced the mortality rate, as evident from the Kaplan–Maier analysis, and improved the wet-to-dry ratio of the lung in contrast to the Lipopolysaccharide-induced group. Following the in vivo studies, computational studies were commenced using molecular docking, molecular dynamic simulation and binding free energy calculations (MM-PBSA/GBSA). The molecular docking results showed that Poncirin interacted with the JNK, ERK, NIK and IL-1[Formula: see text] via multiple hydrogen and hydrophobic bonds. Furthermore, the MD simulation showed that complexes are dynamically stable for 50 ns and 4QTD, and 6Y8M showed maximum stability during simulation. Furthermore, the binding free energy calculation showed favorable binding energies of the ligand–protein complexes. In conclusion, the Poncirin showed marked protection against the lung injury induced by LPS using in vivo and computational studies. However, further studies will be required to employ Poncirin clinically.