Synthetic Pyridoindole and Rutin Affect Upregulation of Endothelial Nitric Oxide Synthase and Heart Function in Rats Fed a High-Fat-Fructose Diet.

Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.

Impact of improving eating habits and rosmarinic acid supplementation on rat vascular and neuronal system in the metabolic syndrome model.

Decreasing high fat and high carbohydrate intake, together with the administration of natural bioactive drugs, is assumed to have a protective effect in the prevention and amelioration of the metabolic syndrome (MetS). The aim of the study was to evaluate effects of diet improvement and/or a phenolic compound (rosmarinic acid; RA) administration (100 mg/kg per d) on metabolic as well as functional changes of vessels and hippocampus caused by the MetS-like conditions. The MetS-like conditions were induced by a high-fat-fructose diet (HFFD) in Prague hereditary hypertriacylglycerolaemic (HTG) rats. The effect of diet improvement and RA administration was studied using biochemical and functional measurements. Consumption of HFFD by HTG rats resulted in the development of conditions like the MetS. The fat and fructose restriction from the diet led to amelioration of basic indicators of metabolic state in rats fed HFFD and to amendment parameters of glucose tolerance test and reduction of the IL-1ß serum levels. Moreover, aortic endothelial function was improved with an impact on blood pressure. The functional measurement of electrophysiology of the hippocampus showed that long-term potentiation of neuronal transmission course deteriorated after HFFD was improved by energy restriction. Oral administration of RA had a supporting effect not only on lipid and glucose metabolism but also on the vascular endothelium. Combination of both types of therapy induced beneficial effect on glucose tolerance and lipid peroxidation. Thus, combined improvement of diet habits and treatment with natural bioactive drugs is assumed to have protective effect in prevention and amelioration of the MetS.