Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice
| Autor: | Kun Tang, XueMeng Chen, Wei Zhang, Xiaoli Xu, Yi Zeng, Ting Ting Liu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Flavonols Anti-Inflammatory Agents Pharmacology medicine.disease_cause Antioxidants Mice chemistry.chemical_compound Hyperlipidemia Endothelial dysfunction Aorta Foam cell Mice Knockout biology Plaque Atherosclerotic Lipoproteins LDL Phenotype Liver Biochemistry Cytokines lipids (amino acids peptides and proteins) Inflammation Mediators medicine.symptom Cardiology and Cardiovascular Medicine Aortic Diseases Inflammation Diet High-Fat 03 medical and health sciences Human Umbilical Vein Endothelial Cells medicine Animals Humans Genetic Predisposition to Disease business.industry Cholesterol Atherosclerosis medicine.disease Disease Models Animal Oxidative Stress RAW 264.7 Cells 030104 developmental biology Receptors LDL chemistry ABCA1 LDL receptor biology.protein Surgery business Oxidative stress Foam Cells |
| Zdroj: | Atherosclerosis. 262:39-50 |
| ISSN: | 0021-9150 |
| Popis: | Background and aims Dihydromyricetin, the most abundant flavonoid in Ampelopsis grossedentata , exerts numerous pharmacological activities, including anti-inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities; however, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of dihydromyricetin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient ( LDLr −/− ) mice. Methods Blood samples were collected for determination of serum lipid profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology, hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation were performed on liver and aorta samples by molecular biology methods. The effects of dihydromyricetin on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation were further studied. Results (1) Dihydromyricetin ameliorated hyperlipidemia, reduced serum ox-LDL, IL-6 and TNF-α levels in HFD-fed LDLr −/- mice. Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and increased protein expressions of PPARα, LXRα and ABCA1. (3) It inhibited atherosclerotic lesion formation and favoured features of plaque stability. (4) Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the reduced IL-6 and TNF-α mRNA expression; (5) it prevented hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in the liver and suppressing reactive oxygen species generation and NOX2 protein expression in both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation and enhanced cholesterol efflux. Conclusions These findings suggest that dihydromyricetin could reduce atherosclerosis via its pleiotropic effects, including improvement of endothelial dysfunction, inhibition of macrophage foam cell formation, amelioration of lipid profiles, anti-inflammatory action and anti-oxidative effect. |
| Databáze: | OpenAIRE |
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