iridoids and Hypercholesterolemia

Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5 % dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5 % dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg × kg(-1) × day(-1). All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol groups. The NMR-based metabonomic study, performed through the analysis of spectroscopic data, depicted differences in the metabolome of the various groups with significant alterations in purine metabolism. In conclusion, the addition of oleuropein to a normal or hypercholesterolemic diet results in a preconditioning-like intracellular effect, eliminating the deleterious consequences of ischemia and hypercholesterolemia, followed by a decrease of oxidative stress biomarkers. This effect is exerted through inducing precondit

Topics: Animals; Cholesterol; Disease Models, Animal; Hypercholesterolemia; Iridoid Glucosides; Iridoids; Male; Malondialdehyde; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Olea; Oxidative Stress; Phosphatidylinositol 3-Kinases; Protective Agents; Rabbits; Signal Transduction; Tyrosine

The lyophilized aqueous extract of Ajuga iva (Ai) is able to reduce oxidative stress, which may prevent lipid peroxidation in hypercholesterolemic rats. Iridoids (I) were isolated from Ai. We hypothesized that the antioxidant defense status in red blood cells (RBC) and tissues in rats fed a cholesterol-rich diet and treated with Ai may be correlated to these compounds. Male Wistar rats (n = 32) weighing 120 +/- 5 g were fed a diet containing 1% cholesterol for 15 days. After this phase, hypercholesterolemic (HC) rats were divided into groups, fed the same diet, and received either the same or different doses (5, 10, or 15 mg/kg body weight by intraperitoneal injection) of I for 15 days. Compared with the HC group, total cholesterol value was 1.4- and 1.2-fold lower in the I(5)-HC and I(10)-HC groups. Serum thiobarbituric acid reactive substance content was 2.3-, 2.9-, and 3-fold lower in the I(5)-HC, I(10)-HC, and I(15)-HC groups compared with the HC group. In RBC, glutathione peroxidase, glutathione reductase, and superoxide dismutase activities were significantly higher in the I(5)-HC, I(10)-HC, and I(15)-HC groups than the HC group. Liver, heart, and muscle glutathione peroxidase and superoxide dismutase activities were significantly higher in the groups treated with I than the HC group. Muscle glutathione reductase activity was increased 1.4-fold in the I(5)-HC, 1.5-fold in the I(10)-HC, and 1.5-fold in the I(15)-HC group. In HC rats, different doses of I increase the antioxidant enzyme activities in RBC and act differently in tissues. Treatment with I may play an important role in suppressing oxidative stress caused by dietary cholesterol and, thus, may be useful for the prevention and/or early treatment of hypercholesterolemia.

Topics: Ajuga; Animals; Anticholesteremic Agents; Antioxidants; Cholesterol, Dietary; Dose-Response Relationship, Drug; Erythrocytes; Hypercholesterolemia; Iridoids; Liver; Male; Muscles; Myocardium; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances

We have investigated the hypolipidemic effects of swertiamarin an active lead isolated from a perennial herb Enicostemma littorale Blume. in high cholesterol fed rats. Swertiamarin (50 and 75 mg/kg) and atorvastatin (50 mg/kg) was given orally daily for seven consecutive day to the high cholesterol feed rats. Serum total cholesterol, triglycerides, low density lipoprotein and very low density lipoprotein were found to be markedly elevated in the high cholesterol fed control rats and these changes were significantly prevented in swertiamarin treated animals. However, there was no significant effect on serum high density lipoprotein level. The 3-hydroxy 3-methyl glutaryl Co A (HMG-Co A) reductase activity was significantly inhibited in swertiamarin and atorvastatin treated groups compared to high cholesterol fed control group. Swertiamarin was also found to increased excretion of fecal bile acid and total sterols compared to control animals. In conclusion our data suggest that swertiamarin possess high antiatherogenic potential and an effective cholesterol lowering agent and inhibition of HMG-Co A reductase may be one of the main mechanisms of hypolipidemic effect of swertiamarin.

Topics: Animals; Bile Acids and Salts; Cholesterol, Dietary; Feces; Gentianaceae; Glucosides; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Hypolipidemic Agents; Iridoid Glucosides; Iridoids; Lipids; Male; Pyrones; Rats; Rats, Sprague-Dawley; Sterols

Oleuropein-rich extracts from olive leaves and their enzymatic and acid hydrolysates, respectively rich in oleuropein aglycone and hydroxytyrosol, were prepared under optimal conditions. The antioxidant activities of these extracts were examined by a series of models in vitro. In this study the lipid-lowering and the antioxidative activities of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts in rats fed a cholesterol-rich diet were tested. Wistar rats fed a standard laboratory diet or cholesterol-rich diets for 16 weeks were used. The serum lipid levels, the thiobarbituric acid reactive substances (TBARS) level, as indicator of lipid peroxidation, and the activities of liver antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) were examined. The cholesterol-rich diet induced hyperlipidemia resulting in the elevation of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). Administration of polyphenol-rich olive leaf extracts significantly lowered the serum levels of TC, TG and LDL-C and increased the serum level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the content of TBARS in liver, heart, kidneys and aorta decreased significantly after oral administration of polyphenol-rich olive leaf extracts compared with those of rats fed a cholesterol-rich diet. In addition, these extracts increased the serum antioxidant potential and the hepatic CAT and SOD activities. These results suggested that the hypocholesterolemic effect of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts might be due to their abilities to lower serum TC, TG and LDL-C levels as well as slowing the lipid peroxidation process and enhancing antioxidant enzyme activity.

Topics: Animals; Antioxidants; beta-Glucosidase; Catalase; Cholesterol, Dietary; Enzyme Activation; Heart; Hydrochloric Acid; Hydrolysis; Hypercholesterolemia; Iridoid Glucosides; Iridoids; Lipid Peroxidation; Lipids; Liver; Male; Molecular Structure; Olea; Organ Size; Phenylethyl Alcohol; Plant Extracts; Plant Leaves; Pyrans; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances