Dihydromyricetin Ameliorates Atherosclerosis In LDL Receptor Deficient Mice And Its Possible Mechanisms

Background and aims:Dihydromyricetin（DMY）,the most abundant flavonoid in Ampelopsis grossedentata,exerts numerous pharmacological activities,including anti-inflammatory,antioxidant,hepatoprotective,and lipid regulatory;however,its protective effect against atherosclerosis remains poorly understood.The aim of the present study was to evaluate the effects of DMY on high fat diet group（HFD）-induced atherosclerosis using LDL receptor deficient(LDLr^-/-)mice.Methods:The blood samples were collected for serum lipid profiles,oxidized LDL（ox-LDL）and pro-inflammatory cytokines determination.Histology,hepatic lipid content,quantification of atherosclerosis,assessment of oxidative stress and inflammation were performed on liver and aorta samples by methods of molecular biology.The effect of DMY on ox-LDL-induced human umbilical vein endothelial cells（HUVECs）dysfunction was further studied.Results:1)DMY slightly reduced the weight of HFD-fed LDLr^-/-mice,but there was no significant difference;2)DMY ameliorated the content of TC,TG and LDL-c and reduced serum ox-LDL,IL-6 and TNF-αlevel in HFD-fed LDLr^-/-mice;3)DMY suppressed hepatic lipid accumulation and increased protein expressions of PPARa,LXRa and ABCA1;4)DMY ameliorated inflammation reaction and reduced mRNA level of CD68,IL-6,TNF-αin HFD-fed LDLr^-/-mice;5)DMY inhibited atherosclerotic lesion formation and favoured features of plaque stability;6)DMY prevented hepatic and aortic inflammation by reducing IL-6 and TNF-αmRNA expression;7)DMY prevented hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in liver and suppressing reactive oxygen species generation and NOX2 protein expression in both liver and aorta;8)DMY inhibited ox LDL-induced injury,monocytes adhesion,apoptosis and oxidative stress in HUVECs.Conclusions:These findings suggest that DMY could reduce atherosclerosis via its pleiotropic effects,including improvement of endothelial dysfunction,amelioration of lipid profiles,anti-inflammatory action and anti-oxidative effect.