Exploring the Effects and Mechanisms of Neohesperidin Dihydrochalcone on Acute Lung Injury in Mice with Sepsis Using Network Pharmacology and Machine Learning

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