Amentoflavone improves cardiovascular dysfunction and metabolic abnormalities in high fructose and fat diet-fed rats

Metabolic syndrome (MS) is a leading cause of mortality and morbidity in Western countries. Amentoflavone (AMF) is a polyphenolic compound which has been found to exhibit various biological activities. In this study, we investigated the protective effects of AMF against cardiovascular and liver dysfunction in high fructose and fat diet (HFFD)-induced MS rats. AMF could evidently inhibit the changes of general metabolic parameters, including body weight, fat mass, insulin level, and glucose tolerance activity. AMF markedly protected against cardiovascular dysfunction, as evidenced by a decrease of systolic blood pressure, left ventricular internal diameter in diastole (LVIDd) and left ventricular posterior wall thickness in diastole (LVPWd); increase of fractional shortening; and decrease of ejection fraction, relative wall thickness, estimated LV mass, cardiac stiffness and LV wet weight in HFFD-fed rats. AMF also inhibited the increase of aortic vasoconstriction in response to phenylephrine and increased relaxation in response to acetylcholine in HFFD-fed rats. AMF reversed the HFFD-induced decrease of nitrogen oxide level, increase of type 1 Ang II receptor (AT-1A) expression and decrease of AT-2A expression. AMF reduced histological and functional injury and lipid accumulation in livers in MS rats. AMF also inhibited HFFD-induced oxidative stress, as reflected by the decrease of thiobarbituric acid reactive substance content, increase of GSH level, increase of superoxide dismutase and catalase activities, and decrease of NADPH oxidase activities. In summary, we showed that AMF exhibited protective effects against cardiovascular dysfunction and liver injury in MS rats. Inhibition of the renin-angiotensin system and oxidative stress contributes to cardiovascular and liver protective activities. Our data provide novel insights into the beneficial effects of AMF against MS.