PR002799 (Project)

Description:Acute inflammation is a fundamental physiological response to tissue damage or microbial invasion. While essential for host defense, chronic or uncontrolled inflammation contributes to various pathologies, including cardiovascular disease, neurodegeneration, and cancer. Functional lipidomics, which analyzes and compares lipid signatures between control and disease/treatment samples, seeks to identify bioactive lipids, molecular targets, or drug candidates that can modulate the lipid profile. Using a phenotypic screening approach based on functional lipidomics, we demonstrate that specific meroterpenoids exert anti-inflammatory effects by interfering with lipid mediator biosynthesis in vitro and in vivo. These compounds induce structure-dependent switches in lipid mediator classes, which also relies on an unexpected connection between lipogenesis and inflammation. Furthermore, Mitrophorone B effectively redirects neutral lipid accumulation, suppresses ferroptosis, and inhibits inflammation. These findings suggest its potential as a promising lead compound for targeting necroinflammatory liver diseases associated with aberrant lipid metabolism.