Fenchone alleviates 7-ketocholesterol-induced oxiapoptophagy through activation of KLF4-PPARγ-Arg1-mediated M2 macrophage signalling

7-ketocholesterol (7KCh), a cytotoxic oxysterol enriched in atherosclerotic plaques, provokes macrophage dysfunction through oxiapoptophagy, a linked process of oxidative stress, apoptosis and autophagy culminating in pro-inflammatory M1 polarization. Targeting this process could mitigate oxysterol-driven vascular inflammation. In this study, murine IC-21 macrophages were induced with 7KCh and co-exposed to fenchone, a bicyclic monoterpene with known anti-inflammatory properties. Cellular oxidative stress, apoptosis and autophagy were assessed by spectrofluorometric and cytometric assays. Expression of key mediators (iNOS, COX2, HO1, Casp3, Bcl2, LC3B, PARP1, Arg1, KLF4 and PPARγ) was quantified by RT-qPCR and western blotting. Molecular docking was used to identify interactions of fenchone with KLF4 and PPARγ. The results showed that 7KCh significantly increased ROS and NO …