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

• Published in: Atherosclerosis 2018-01, Vol.268, p.207-214
• Main Authors: Christodoulou, Ei, Kadoglou, N.P.E., Stasinopoulou, M., Konstandi, O.A., Kenoutis, C., Kakazanis, Z.I., Rizakou, A., Kostomitsopoulos, N., Valsami, G.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacokinetics; Anti-Inflammatory Agents - pharmacology; Aorta - drug effects; Aorta - metabolism; Aorta - pathology; Aortic Diseases - blood; Aortic Diseases - genetics; Aortic Diseases - pathology; Aortic Diseases - prevention & control; ApoE−/− mice; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - genetics; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Crocetin; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - etiology; Diet, High-Fat; Dose-Response Relationship, Drug; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - pharmacology; Inflammation; Inflammation Mediators - metabolism; Male; Mannose-Binding Lectins - chemistry; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Mice, Inbred C57BL; Mice, Knockout, ApoE; Plant Extracts - isolation & purification; Plant Extracts - pharmacokinetics; Plant Extracts - pharmacology; Plant Lectins - chemistry; Plaque, Atherosclerotic; Rupture, Spontaneous; Saffron; Triglycerides - blood
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2017.10.032

We aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE−/−) mice. 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. 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