Crocus sativus L. aqueous extract reduces atherogenesis, increases atherosclerotic plaque stability and improves glucose control in diabetic atherosclerotic animals

Abstract Background and aims We aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout ( ApoE −/− ) mice. Methods Fifty male, ApoE −/− mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks). After blood sampling and euthanasia, aortic roots were excised and analyzed for gene expression and/or percentage of aortic stenosis, relative content of macrophages, smooth muscle cells (SMCs), connective tissue, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases-2,-3,-9 (MMP-2,-3,-9) and their inhibitor (TIMP-2) and IL-6. SFE doses were determined by a pilot serum pharmacokinetic study in C57BL/6J wild-type mice. Results SFE did not affect body weight and total cholesterol levels ( p  > 0.05), while high SFE dose significantly ameliorated glucose and triglycerides profiles compared to other groups ( p p p 30%) in IL-6, TNF-α, MCP-1, MMP-2,-3,-9 ( p Conclusions SFE exerted dose-dependent anti-atherosclerotic and plaque-stabilizing effects in Apo-E −/− mice, probably mediated by a favorable modification of inflammatory mechanisms, which requires further investigation.