High-cholesterol Diet Control Research Articles

The beneficial effects of virgin olive oil against oxidative stress induced by hypercholesterolemia in rats

Cardiovascular disease (CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects. This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard food and receiving by gavage virgin olive oil (HCD+VOO) and (4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low–Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High–Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

Effect of Lactobacillus fermentum MCC2760-Based Probiotic Curd on Hypercholesterolemic C57BL6 Mice.

Lactobacillus fermentum MCC2760 is a probiotic strain proven earlier for cholesterol-reducing and anti-inflammatory properties in vitro and in vivo. This study investigates L. fermentum MCC2760-based probiotic curd in high-cholesterol diet (HCD)-fed C57BL6 mice. The mice were grouped into normal diet control, high-cholesterol diet control, normal diet with probiotic supplementation, and high-cholesterol diet with probiotic supplementation. Control groups and treatment groups were supplemented with market curd and probiotic curd, respectively, via oral gavage for eight weeks. The probiotic count was maintained at 10.95 log CFU/mL in the developed probiotic curd. The HCD group showed an increase in feed intake and body weight. Reduction in the levels of serum cholesterol, triglycerides, low-density lipoprotein cholesterol, glucose, aspartate aminotransferase, and alanine transaminase was observed in probiotic-supplemented groups. The probiotic-supplemented group resulted in an increase in Lactobacillus spp. count along with reduced pathogen count in the feces. Probiotic supplementation also showed a reduction in the bacterial translocation count in mesenteric adipose tissue. Expression of inflammatory markers by qPCR showed the decline in the fold change of TNF-α, IL-6, and IL-12 and elevation in the fold change of IL-10 in the adipose tissue of the probiotic-treated group. Probiotic supplementation also improved the expression of GLP-1, ZO-1, and CB2 in the intestine. They were thus possibly playing a role in the enhancement of barrier function. Histopathological sections showed improvement in the cellular infiltration and pathological indications due to the high-cholesterol diet intake. Our study also confirmed that probiotics could increase serum antioxidant enzymes in treated groups, showing their beneficial antioxidant activity. It suggests the anti-inflammatory, antioxidant effect, and gut barrier function of the given probiotic formulation, which ameliorate hypercholesterolemia.

Efficacy of nobiletin in improving hypercholesterolemia and nonalcoholic fatty liver disease in high-cholesterol diet-fed mice

BACKGROUND/OBJECTIVESNobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice.SUBJECTS/METHODSC57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks.RESULTSHCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers.CONCLUSIONSThe present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

The cholesterol-lowering activity of miracle fruit (Synsepalum dulcificum).

Miracle fruit (Synsepalum dulcificum) is famous for its uniqueness of modifying sour taste to sweetness. However, its cholesterol-lowering activity has not been reported. This study investigated the effect of S. dulcificum on the compositional changes of plasma lipids in hamsters fed a high-cholesterol control diet. Six groups of hamsters were fed either a control diet or one of the five experimental diets containing 2% ethanol extract of leaves, 2% water extract of leaves, 2% ethanolic extract of seeds (ES), 2% water extract of seeds, or 2% dry pulp. Results showed that ES decreased the plasma total cholesterol (TC). Two triterpenoids (lupeol acetate and β-amyrin acetate) were isolated from the ES and they added to a diet could decrease TC by 15%-20% in hamsters. It was concluded that ES showed potent TC-lowering activity and triterpenoid was one of the active components of ES. PRACTICAL APPLICATIONS: In recent years, people are more interested in phytochemicals from functional foods treated for hyperlipidemia because they possessed fewer side effects than the synthetic drugs. The triterpenoids isolated from the miracle fruit may be promising candidates for the development of cholesterol-lowering agent, especially for patients whose blood cholesterol level and body weight are high. Meanwhile, the miracle fruit have a good potential as cholesterol-lowering functional food or a natural source of cholesterol-lowering agent.

Anti-Atherosclerotic and Anti-Inflammatory Effects of Curcumin on Hypercholesterolemic Male Rabbits.

Curcumin has a potent antioxidant and anti-inflammatory properties that may suppress inflammatory component of atherosclerosis. It has been demonstrated that curcumin derivatives can reduce the formation of arterial fatty streaks in cholesterol-fed rabbits. Therefore in this study we evaluated the protective effects of Curcumin on the progression of atherosclerosis. 20 mature rabbits were included for this study; they were randomly divided into four groups each of 5. Group 1: (normal control) were fed corn pellets diet and tab water, group 2: (high cholesterol diet control) were kept on cholesterol rich diet (2% cholesterol) and tab water. Group 3: (cholesterol and rosuvastatin treated group) were kept on cholesterol rich diet (2% cholesterol) and 2.5mg/kg/day Rosuvastatin dispersed in DW and given orally, group 4: (cholesterol and curcumin treated group) were kept on cholesterol rich diet (2% cholesterol) and 0.2% curcumin added with corn pellets. The study continued for 12weeks then assessment of serum level of high sensitive C-reactive protein, ICAM1, VCAM1 and PCSK9 was carried out at the end of the study. Total antioxidant activity of curcumin was also determined. Histopathological examination of aortic tissues for atherosclerotic changes was also carried out. Atherogenic (cholesterol rich diet) induced an increment in serum level of TC, LDL, VLDL and TG with concomitant decrement in serum level of HDL and increased atherogenic index. Treatment with curcumin produced substantial reduction in serum TC, LDL, TG with no effect on HDL level thus decreased atherogenic index. Rabbits treated with curcumin showed a significant reduction in the serum level of high sensitive C-reactive protein, ICAM1, VCAM, PCSK9 serum expression and aortic total antioxidant capacity. Curcumin has a potent anti-inflammatory and anti- oxidant effects against atherosclerosis so exerts a protective role by decreasing lipid oxidation and inflammatory markers.

Isoflavones enhance the plasma cholesterol-lowering activity of 7S protein in hypercholesterolemic hamsters.

Previous studies have shown that 7S protein is the active ingredient responsible for the plasma cholesterol-lowering activity of soybean. It is hypothesized that isoflavones in soybean could enhance the blood cholesterol-lowering activity of 7S protein. Forty-eight hamsters were divided into six groups and fed a non-cholesterol diet or one of the five high-cholesterol diets containing 12.1% 7S protein with 0-15.62 mg g-1 isoflavones. The results showed that addition of isoflavones in diets dose-dependently enhanced the plasma total cholesterol-lowering activity of 7S protein. Addition of isoflavones in 7S protein-based diets significantly reduced hepatic cholesterol accumulation by 12.6-26.1%, compared with the high cholesterol control diet. Isoflavones could also facilitate excretion of neutral sterols in a dose-dependent manner. Supplementation of isoflavones in diets favourably modulated mRNA expression and the protein mass of HMG-CoA reductase. It was concluded that the enhancing effect of isoflavones on the blood cholesterol-lowering activity of 7S protein was mediated by inhibiting the cholesterol absorption and de novo cholesterol synthesis in hypercholesterolemic hamsters.

Wild Lonicera caerulea berry polyphenol extract reduces cholesterol accumulation and enhances antioxidant capacity in vitro and in vivo

The hypocholesterolemic effect of Lonicera caerulea berry extract rich in polyphenols (LCBP) on high cholesterol-induced hypercholesterolemia and lipoprotein metabolite changes was examined in Caco-2 cells and rats. Cyanidin-3-glucoside, catechin, and chlorogenic acid are the major phenolic components of LCBP. The cholesterol-reducing effect and antioxidant capacity of these components were compared in Caco-2 cells. LCBP (80 μg/mL) and cyanidin-3-glucoside, catechin, and chlorogenic acid (50 μM) were found to be effective (p < 0.05). Rats were fed a high cholesterol diet (HCD) with or without LCBP supplementation (75, 150, and 300 mg/kg body weight intragastrically once daily) for 12 weeks. Compared with the HCD control group, LCBP supplementation at 150 and 300 mg/kg decreased the levels of TC, TG, and LDL-C, but increased that of HDL-C. LCBP treatment promoted greater neutral and acidic sterol excretion (p < 0.05) and improved the antioxidant capacity of the colon tissue, colon contents, and blood. Moreover, trimethylamine N-oxide (TMAO) levels were decreased in serum (p < 0.05). NPC1L1, ACAT2, and MTP mRNA and protein expression were reduced and ABCG5/8 expression was increased (p < 0.05) after LCBP treatment. Our results suggest that LCBP could be used as a functional food for the prevention and treatment of diseases related to excessive cholesterol accumulation.

Cranberry anthocyanin as an herbal medicine lowers plasma cholesterol by increasing excretion of fecal sterols

BackgroundInterest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. HypothesisThe present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion. MethodsForty-four hamsters were randomly divided into five groups and fed one of the five diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD), a HCD diet supplemented with a low dose of 1% CrA (CL), a HCD diet supplemented with a high dose of 2% CrA (CH), and a HCD diet supplemented with 0.5% cholestyramine as a positive control drug (P-CTL), respectively, for six weeks. Plasma lipoprotein cholesterol was quantified using the enzymatic kits, while the gene expressions of transporters, enzymes and receptors involved in cholesterol absorption and metabolism were quantified using the quantitative RT-PCR. Fecal sterols were quantified using gas chromatography (GC). ResultsPlasma total cholesterol and aorta atherosclerotic plaque decreased dose-dependently with the increasing amounts of CrA added into diets. This was accompanied by a dose-dependent increase in excretion of both neutral and acidic sterols. CrA had no effect on the mRNA levels of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl CoA:cholesterol acyltransferase2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5) as well as hepatic cholesterol-7α-hydroxylase (CYP7A1), 3-Hydroxy-3-methylglutaryl reductase (HMG-CoA-R), sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDL-R), and Liver X receptor alpha (LXRα). ConclusionCrA as an herbal medicine could favorably modify the lipoprotein profile in hamsters fed a high cholesterol diet by enhancing excretion of fecal neutral and acidic sterols, most likely not mediated by interaction with genes of transporters, enzymes and proteins involved in cholesterol absorption and metabolism.

Hypolipidemic effects of HVC1 in a high cholesterol diet‑induced rat model of hyperlipidemia.

HVC1, a novel formation containing four herbs, was developed and its hypolipidemic effects in rats with high cholesterol diet (HCD)-induced hyperlipidemia were investigated. The rats were given a HCD for 8 weeks. The HVC1-treated groups were orally administered HVC1 at doses of 10, 50 or 250 mg/kg, respectively, and the simvastatin group was treated at a dose of 10 mg/kg. The normal diet and HCD control groups were administered with physiological saline. Oral administration of HVC1 (10, 50 or 250 mg/kg) significantly reduced the body weight of rats with hyperlipidemia and regulated the total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in the serum. In addition, tissue analysis revealed that lipid accumulation in the liver and aorta was reduced by HVC1 administration. Furthermore, HVC1 significantly reduced the mRNA expression of peroxisome proliferator-activated receptor-γ, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor, as well as the protein level of 5′ adenosine monophosphate-activated protein kinase in the liver. The results clearly demonstrate that HVC1 has a potent hypolipidemic effect, and suggest that HVC1 should be evaluated as a potential treatment for hyperlipidemia.

Alcohol modulates autophagy and apoptosis in pig liver tissue

BackgroundAutophagy serves as a cellular protective mechanism against alcohol-induced tissue injury but excessive autophagy can also be detrimental leading to apoptosis. Our laboratory has previously shown that moderate alcohol consumption alters expression of proteins in the insulin signaling pathway and worsens glucose metabolism in the liver in a swine model of metabolic syndrome. We examined the effect of alcohol consumption on apoptosis and autophagy signaling in the liver in our clinically relevant animal model of chronic hypercholesterolemia. Material and methodsTwenty-six Yorkshire swine were fed a high-fat diet for 4 wks and were then split into three groups: hypercholesterolemic diet alone (HCC, n = 9), hypercholesterolemic diet with vodka (hypercholesterolemic vodka [HCV], n = 9), and hypercholesterolemic diet with wine (hypercholesterolemic wine [HCW], n = 8) for 7 wks. Animals underwent euthanasia, and liver tissue samples were harvested for analysis. Liver tissue was analyzed via Western blot analysis. Protein density data were normalized to GAPDH and is reported as fold-change values ± standard error of the mean compared to the high-cholesterol diet control group. A Kruskal–Wallis test with a Dunn's multiple comparison test was used to compare the means among groups. ResultsThe HCV group showed significant increases in several proapoptotic proteins (including caspase 3, caspase 8, caspase 9, and cleaved caspase 9) compared with the HCC group. There was a decrease in the proapoptotic protein (BAD) and an increase in anti-apoptotic signal (B-cell lymphoma-2) in the HCW group compared with HCC control. There were increases in pro-survival proteins (AKT, p-AKT, mTOR, p-mTOR) in the HCW and the HCV group compared with control (HCC). There were decreases in autophagy protein LCB-3 in the HCW and HCV compared with the control. ConclusionsWe found that moderate alcohol consumption altered protein expression related to apoptosis and autophagy signaling in pig liver in the setting of hypercholesterolemia. Interestingly, vodka may induce proapoptotic pathways in liver tissue, whereas wine may induce anti-apoptotic signaling. These results provide a mechanism by which vodka may contribute to alcoholic liver disease and supports the notion that wine, containing resveratrol, may prevent cellular apoptosis in liver tissue in the setting of hypercholesterolemia.

Anti-Aging and Tissue Regeneration Ability of Policosanol Along with Lipid-Lowering Effect in Hyperlipidemic Zebrafish via Enhancement of High-Density Lipoprotein Functionality.

We investigated the tissue regeneration and lipid-lowering effects of policosanol (PCO) by employing a hyperlipidemic zebrafish model. A reconstituted high-density lipoprotein containing policosanol (PCO-rHDL) facilitated greater cell growth and replication with less apoptosis and reactive oxygen species (ROS) production in BV-2 microglial cell lines. From in vivo study, injection of rHDL containing apolipoprotein A-I (ApoA-I) caused 76 ± 4% (p = 0.01) greater tissue regeneration activity than the phosphate-buffered saline (PBS) control, whereas PCO-rHDL caused 94 ± 7% (p = 0.002) increased regeneration. PCO in ethanol (EtOH) showed lower cholesteryl ester transfer protein (CETP) inhibitory ability than did anacetrapib, whereas PCO-rHDL showed higher inhibitory ability than anacetrapib, suggesting a synergistic effect between PCO and rHDL. Following 9 weeks of PCO consumption, the PCO group (0.003% PCO in Tetrabit) showed the highest survivability (80%), whereas normal diet (ND) and high-cholesterol diet (HCD) control groups showed 67% and 70% survival rates, respectively. Supplementation with a HCD resulted in two-fold elevation of CETP activity along with 3- and 2.5-fold increases in serum total cholesterol (TC) and triglycerides (TGs) levels, respectively. Consumption of PCO for 9 weeks resulted in 40 ± 5% (p = 0.01 vs. HCD) and 33 ± 4% (p = 0.02 vs. HCD) reduction of TC and TGs levels, respectively. Serum high-density lipoprotein cholesterol (HDL-C) level increased up to 37 ± 2 mg/dL (p = 0.004), whereas the percentage of HDL-C/TC increased up to 20 ± 2% from 5 ± 1% compared to the HCD control. The serum glucose level was reduced to 47 ± 2% (p = 0.002) compared to the HCD control. Fatty liver change and hepatic inflammation levels were remarkably increased upon HCD consumption and were two-fold higher than that under ND. However, the PCO group showed 58 ± 5% (p = 0.001) and 50 ± 3% (p = 0.006) reduction of inflammation enzyme levels and lipid content in hepatic tissue under HCD. In conclusion, PCO supplementation showed lipid-lowering and HDL-C-elevating effects with ameliorating fatty liver change. These in vivo anti-atherosclerotic and anti-diabetic effects of PCO are well associated with in vitro anti-apoptotic activities.

Effects of combined extract of cocoa, coffee, green tea and garcinia on lipid profiles, glycaemic markers and inflammatory responses in hamsters.

BackgroundDyslipidaemia is highly associated with cardiovascular and cerebrovascular diseases, which have been ranked second and third place of leading causes of death in Taiwan. Some plant extracts have been proved effective against dyslipidaemia. However, the combination of plant extracts was rarely studied. The purpose of the present study is to understand the beneficial effects of a combined extract (comprising cocoa, coffee, green tea and garcinia; CCGG) on lipid profiles in serum, liver, and faeces as well as glycaemic markers and related proinflammatory cytokines by using an appropriate animal model, the golden Syrian hamster.MethodsA total of 40 male hamsters were randomly assigned to five groups: (1) vehicle control, (2) high-cholesterol diet control, (3) high-cholesterol diet of 311 mg/kg/d of CCGG, (4) high-cholesterol diet of 622 mg/kg/d of CCGG and (5) high-cholesterol diet of 1555 mg/kg/d of CCGG. At the end of the experiment, blood, tissue and faecal samples were collected for further analysis.ResultsAfter 6 weeks of treatment, CCGG supplementation significantly reduced serum lipid content (triglycerides, total cholesterol and LDL-C) and hepatic lipid content (triglycerides and cholesterol) with dose-dependent effects. In addition, an increase in excretion of faecal lipids (bile acids) was observed after supplementation. Furthermore, the homeostasis model assessment of insulin resistance (HOMA-IR) index and serum proinflammatory cytokine levels (TNF-α and IL-6) involved in dyslipidaemia was markedly improved. In addition, by monitoring biochemical parameters as well as histopathology of major tissues, no toxicity was observed after the consumption of CCGG.ConclusionDietary CCGG supplementation may exert potential effects on ameliorating hyperlipidaemia, insulin resistance, liver steatosis and related inflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0806-1) contains supplementary material, which is available to authorized users.

Anti-hyperlipidemic and anti-atherosclerotic effects of Pinus eldarica Medw. nut in hypercholesterolemic rabbits.

BackgroundPrevious studies suggest that chemical constituents present in Pinus eldarica Medw (P. eldarica) nut possess antioxidant properties that may positively influence lipid profile.The present study was conducted to evaluate the efficacy of P. eldarica nut on the experimental atherosclerosis development in hypercholesterolemic rabbits.MethodsForty male 6 months old white New Zealand rabbits (1.8–2 kg) were randomly assigned into five equal groups. One group was kept as control (normal) group, fed on standard rabbit diet and other 4 groups were fed on high cholesterol diet (HCD). Out of four HCD groups one group was kept as control (HCD) and other three groups were treated with different doses (50, 100 and 200 mg/kg/day) of P. eldarica nut for 8 weeks. Percentage of aortic wall area changes as indication of atherosclerosis development and fasting blood cholesterol, LDL, HDL and triglyceride levels were determined in all groups.ResultsThe results indicate that fasting blood cholesterol and aortic atherosclerotic involvements in 200 mg/kg/day and 100 mg/kg/day P. eldarica nut extract treated groups significantly decreased as compared to the high cholesterol-diet control group.ConclusionP. eldarica nut lowers blood cholesterol level and aortic atherosclerotic involvement in hypercholesterolemic rabbits.

Baicalin inhibits the expression of monocyte chemoattractant protein-1 and interleukin-6 in the kidneys of apolipoprotein E-knockout mice fed a high cholesterol diet.

Hyperlipidemia is considered an independent risk factor for renal dysfunction and induces a significant increase in the expression of inflammatory mediators, which can be used to evaluate the degree of renal injury. Baicalin is widely used in traditional Chinese herbal medicine and has multiple pharmacological effects. The present study investigated whether baicalin can attenuate the expression of vascular cell adhesion molecule 1 (VCAM‑1) via a reduction in the expression of monocyte chemoattractant protein‑1 (MCP‑1) and interleukin‑6 (IL‑6) in the kidney of apolipoprotein E (ApoE)‑knockout (KO) mice fed a high cholesterol diet. These mice were used as a model of atherosclerosis and were treated with baicalin (100 mg/kg/day) daily by gavage for a period of 12 weeks. By contrast, wild‑type male C57BL/6J mice were fed a standard diet. Blood samples were obtained from the angular veins of the mice to measure the total cholesterol (TC) and the expression levels of VCAM‑1, MCP‑1 and IL‑6 in the kidney tissues of the mice were analyzed using reverse transcription quantitative polymerase chain reaction and western blot analysis. Following oral administration of baicalin, no significant difference was observed in the TC in the baicalin group compared with the high cholesterol diet control group. The TC was significantly higher in the AopE‑KO mice compared with the wild‑type male C57BL/6J mice. The expression levels of VCAM‑1, MCP‑1 and IL‑6 in the kidney tissues of the baicalin group were lower compared with those in the high cholesterol diet control group. The results suggested that baicalin decreased the expression levels of pro‑inflammatory mediators and prevented kidney dysfunction in the ApoE‑KO mice fed a high cholesterol diet.

Antioxidant and anti-inflammatory effects of Marrubium alysson extracts in high cholesterol-fed rabbits

The antioxidant and anti-inflammatory effects of hexane (HEXA), chloroform (CHLORO), ethyl acetate (EA) and total alcoholic (T. ALCOH) extracts of Marrubium alysson in hypercholesterolemic-fed rabbits were evaluated. Hypercholesterolemia was induced in male rabbits by high cholesterol diet (HCD) (350mg/kg) for 8weeks. Hypercholesterolemic rabbits were allocated into groups, treated with simvastatin (SIM 5mg/kg), different extracts of M. alysson at two doses of 250, 500mg/kg. A normal control group and an HCD control one were used for comparison. Lipid profile, as well as oxidized low density lipoprotein-cholesterol (ox-LDL-C), myeloperoxidase activity (MPO) and superoxide anion production (O2−), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were also evaluated. In addition, histological examination of ascending aorta was performed. We found dyslipidemia associated with significant increases in ox-LDL-C 123.5±9.8nmol MDA/mg non-HDL, MPO activity 0.08±0.05U/100mg tissue and O2− production 3.5±0.3nmol cytochrome C reduced/min/g tissue×10−4 in hypercholerterolemic rabbits. In addition, there was a significant increase in CRP 6.6±0.49μmol/L and MCP-1 190.9±6.4pg/ml and its mRNA expression in HCD. Intima appeared thick with thick plaques surrounding the intima and luminal narrowing. SIM, EA and HEXA extracts of M. alysson had lipid lowering effect, decrease in ox-LDL-C, MPO, O2−, CRP and MCP-1 mRNA expression with improvement of the pathological picture. M. alysson enhanced the stability of plaque, had lipid lowering, anti-inflammatory and antioxidant activities.

Effects of Ilex latifolia and Camellia sinensis on Cholesterol and Circulating Immune Complexes in Rats Fed with a High‐Cholesterol Diet

Hypercholesterolaemia is one of the risk factors for atherosclerosis and subsequent cardiovascular disease. Here, we investigated the effects of dietary supplementation with Ilex latifolia or green tea (Camellia sinensis) on the levels of plasma total cholesterol, high-density lipoprotein cholesterol and circulating immune complexes in Sprague Dawley rats fed with a high-cholesterol diet. We demonstrated that daily administration by gavage of I. latifolia or C. sinensis at doses of 1.0 or 2.0 g/kg body weight for 30 days resulted in a significant decrease in plasma total cholesterol levels and circulating immune complexes and an increase in high-density lipoprotein cholesterol in rats fed with a high-cholesterol diet compared with levels in the high-cholesterol diet control group. C. sinensis was more effective than I. latifolia. I. latifolia and C. sinensis could be used as food supplements to protect against the development of hypercholesterolaemia.

Hypocholesterolemic activity of onion is mediated by enhancing excretion of fecal sterols in hamsters

Onion has been shown to favorably modify the lipoprotein profile. However, research on its underlying mechanism is lacking. The present study investigated the interaction of dietary onion powder with the protein expression of key receptors and enzymes involved in cholesterol metabolism. Thirty-six male hamsters were randomly divided into three groups and fed a high-cholesterol control diet or the two experimental diets supplemented with 1% onion powder (OP-1) or 5% onion powder (OP-5), for a period of 8 weeks. It was found that onion dose-dependently decreased plasma total cholesterol (TC) level. The change in plasma lipoprotein profile was accompanied by a greater excretion of both fecal neutral and acidic sterols. Western blot analysis revealed that onion up-regulated sterol regulatory element binding protein 2 (SREBP-2), liver X receptor alpha (LXRα) and cholesterol-7α-hydroxylase (CYP7A1) with no effect on 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and LDL receptor (LDL-R). It was concluded that the hypocholesterolemic activity of onion powder was mediated by enhancement of fecal sterol excretion and up-regulation of LXRα and CYP7A1.

Chronic exercise reduces adhesion molecules/iNOS expression and partially reverses vascular responsiveness in hypercholesterolemic rabbit aortae

To investigate exercise effects on the vascular function in hypercholesterolemia, male New Zealand White rabbits were divided into four groups; i.e. the normal diet control, the high cholesterol diet control, normal diet with exercise, and high cholesterol diet with exercise. High cholesterol diet groups were fed 2% cholesterol rabbit chow for 8 weeks. Animals of exercise groups ran on a treadmill at 0.88 km/h for 10–60 min/day, 5 day/week, and 8 weeks in total. Thoracic aortae were, then, isolated for functional and immunohistochemical analysis. We found that in rabbit aortae, (1) high cholesterol diet feeding caused lipid deposition and intimal thickening, induced expression of P-selectin, VCAM-1, MCP-1 and iNOS, and impaired acetylcholine (ACh)-evoked vasorelaxation; (2) exercise significantly reduced the protein expression of adhesion molecules/iNOS, and the intimal thickness in hypercholesterolemia; (3) chronic exercise enhanced ACh-evoked vasorelaxation in normal rabbits, but it only significantly improved vascular responses to the high dose (10 −6 M) of ACh in hypercholesterolemic rabbits; (4) both exercise and diet effects on vascular responses were mediated by altering the release of NO and endothelium-derived hyperpolarization factor. We conclude that exercise training decreases the expression of adhesion molecules and iNOS, and ameliorates the severe vascular dysfunction induced by high cholesterol feeding.

Cholesterol metabolism in monocyte-derived macrophages from macrophage colony-stimulating factor administered rabbits

The metabolism of ß-very-low-density lipoproteins (ß-VLDL) in macrophages from the blood monocytes of rabbits, which had been administered macrophage colony-stimulating factor (M-CSF) in vivo, was investigated in order to clarify the mechanism of the suppressive effect of M-CSF on cholesterol accumulation in macrophages. Cholesterol ester content after incubation with ß-VLDL, and [ 3H]cholesterol oleate-ß-VLDL incorporation remarkably increased in cultured macrophages from blood monocytes in the high cholesterol diet control group compared to those in the normal diet control group. Those in macrophages from M-CSF-treated groups, both normal diet and high cholesterol diet, were the same as in the normal diet control group. The ratio of released [ 3H]cholesterol to incorporated [ 3H]cholesterol oleate-ß-VLDL in macrophages from control was smaller than that from the M-CSF group. The acyl-coenzyme A:cholesterol acyltranseferase (ACAT) activity was enhanced in the high cholesterol diet groups, and the activity in M-CSF-treated groups decreased. The neutral cholesterol esterase activity was enhanced in the M-CSF-treated groups compared with that in the non-treated control groups. These results suggest that high cholesterol diet induced further cholesterol esterification and that M-CSF treatment enhanced cholesterol clearance in macrophages.