Exploring the Effects and Mechanisms of Neohesperidin Dihydrochalcone on Acute Lung Injury in Mice with Sepsis Using...

Neohesperidin dihydrochalcone (NHDC) is a synthetic sweetener derived from neohesperidin and can improve pathological changes in sepsis-associated acute lung injury (SALI), but the mechanism by which NHDC inhibits SALI remains unclear. We evaluated the therapeutic effect of NHDC (100 mg/kg) and its potential mechanism using bioinformatics approaches with a Lipopolysaccharide (LPS)-induced SALI model (LPS: 10 mg/kg) in mice (n = 6). Bioinformatics analysis identified 176 shared targets between NHDC and SALI, which were enriched in the MAPK signaling pathway. Further screening yielded five key targets (MAPK14, MAPK8, KDR, CASP3, and RHOA) with significant clinical expression differences (p < 0.01). Molecular docking suggested that NHDC could bind to all five targets, with binding energies <-5.0 kJ/mol, and molecular dynamics indicated stable binding between NHDC and MAPK8 (total binding energy ΔG = -181.320 kJ/mol). In vivo, NHDC reversed oxidative stress markers (catalase, superoxide dismutase, glutathione, malondialdehyde, and reactive oxygen species), decreased TNF-α and IL-6 levels, and alleviated lung pathological injury (p < 0.05 vs. model group); it also significantly decreased phosphorylation of mitogen-activated protein kinases(MAPK) pathway proteins (p < 0.001 vs. model group). In summary, our research revealed that NHDC decreased the oxidative stress and inflammatory response of SALI; its specific mechanism is associated with the MAPK pathway. NHDC has a lot of potential as a medication for anti-SALI treatment.