An oxidized mogrol derivative alleviates LPS-induced acute lung injury in association with reduced NLRP3 inflam-masome-associated inflammatory responses in mice

Mogrosides, natural products derived from Siraitia grosvenorii, have been shown to exhibit protective effects against ALI, but structural optimization of their aglycone moiety, mogrol may provide opportunities to improve pharmacological efficacy. In this study, oxidized mogrol de-rivatives (MG-COOH and MG-CHO) were synthesized, and their anti-inflammatory activities were initially compared with those of natural mogrosides in lipopolysaccha-ride (LPS)‑stimulated MH-S cells.

MG-COOH displayed the strongest activity among the compounds and was designated for comprehensive analysis of its protective po-tential and underlying mechanisms in the LPS-induced ALI model. MG-COOH effec-tively alleviated LPS-induced injury in lung, decreased pro-inflammatory cytokine re-lease, and reduced oxidative stress, showing greater efficacy than natural mogrosides. Transcriptomic analysis indicated that MG-COOH modulated genes involved in NF-κB, MAPK, PI3K-Akt, JAK-STAT, and NOD-like receptor pathways.