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The metabolism of choline (highly present in animal products) can produce trimethylamine N-oxide (TMAO), a metabolite with atherosclerotic effects; however, dietary fiber may suppress this metabolic pathway. This study aimed to develop a dietary pattern predictive of plasma TMAO and choline concentrations using reduced rank regression (RRR) and to evaluate its construct validity. Diet and plasma concentrations of choline (μmol/L) and TMAO (μmol/L) were assessed in 1724 post-menopausal women who participated in an ancillary study within the Women's Health Initiative Observational Study (1993–1998). The TMAO dietary pattern was developed using RRR in half of the sample (Training Sample) and applied to the other half of the sample (Validation Sample) to evaluate its construct validity. Energy-adjusted food groups were the predictor variables and plasma choline and TMAO, the response variables. ANCOVA and linear regression models were used to assess associations between each biomarker and the dietary pattern score. Discretionary fat, potatoes, red meat, and eggs were positively associated with the dietary pattern, while yogurt, fruits, added sugar, and starchy vegetables were inversely associated. Mean TMAO and choline concentrations significantly increased across increasing quartiles of the dietary pattern in the Training and Validation samples. Positive associations between the biomarkers and the TMAO dietary pattern were also observed in linear regression models (Validation Sample: TMAO, adjusted beta-coefficient = 0.037 (p-value = 0.0088); Choline, adjusted beta-coefficient = 0.011 (p-value = 0.0224). We established the TMAO dietary pattern, a dietary pattern reflecting the potential of the diet to contribute to plasma concentrations of TMAO and choline. • A diet pattern was created in post-menopausal women to predict plasma biomarkers. • The biomarkers used for development were trimethylamine N-oxide and choline. • The diet pattern consists of high intake of fat, red meat, and eggs. • The diet pattern consists of low intake of yogurt, fruit, and starchy vegetables. • The construct validity of this proposed atherogenic diet pattern was demonstrated. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to develop an improved and more reliable atherogenic diet-induced model of hyperlipidemia in Wistar rats for a better insight into pathophysiological changes and their effects on relevant biochemical and histological markers as well as on the thickness of the abdominal aorta. Methods: The study was conducted on a total number of 24 Wistar rats, three-month-old, weighing 180–230g that were divided into two groups: the standard rodent diet (SD) group (n = 12; 6 males and 6 females) in which rats were fed with commercially available standard rodent diet (SRD), and the atherogenic rodent diet (AD) group (n = 12; 6 males and 6 females) in which rats were fed with our mixture of atherogenic rodent diet (ARD) throughout the study period of 28 days. The body weight of rats was recorded weekly. The blood samples were collected by cardiac puncture and values of total cholesterol (TC) and triglycerides (TG) were determined at baseline, after the 14 days, and on the last day of the study, while other parameters high-density lipoprotein (HDL) cholesterol, lowdensity lipoprotein (LDL) cholesterol, non-HDL cholesterol, total protein (TP), glucose (GC), alanine transaminase (ALT), and aspartate transaminase (AST) were determined only on the last day of the study. The liver and abdominal aorta were collected after sacrifice and stored for further analysis. Results: Feeding rats with an ARD for 14 days resulted in the successful development of hyperlipidemia, as the TC and TG values were significantly increased (p < 0.05). Further feeding with an ARD for a total of 28 days resulted in significantly increased levels of TC, TG, LDL, non-HDL, and decreased levels of HDL compared to rats fed with SRD (p < 0.05). Greater risk predispositions for CVDs were documented for rats in the AD group, due to the significant increase in AI and LDL/HDL ratio compared to the SD group (p < 0.05). Conclusion: Obtained lipid profile and predictors confirm the establishment of a diet-induced model of hyperlipidemia in Wistar rats and prove the suitability of our model for future testing and proving the effectiveness of lipid-lowering agents.

Knowledge of the benefits of mTOR inhibition concerning adipogenesis and inflammation has recently encouraged the investigation of a new generation of mTOR inhibitors for non-alcoholic steatohepatitis (NASH). We investigated whether treatment with a specific mTORC1/C2 inhibitor (Ku-0063794; KU) exerted any beneficial impacts on experimentally-induced NASH in vitro and in vivo. The results indicated that KU decreases palmitic acid-induced lipotoxicity in cultivated primary hepatocytes, thus emerging as a successful candidate for testing in an in vivo NASH dietary model, which adopted the intraperitoneal KU dosing route rather than oral application due to its significantly greater bioavailability in mice. The pharmacodynamics experiments commenced with the feeding of male C57BL/6 mice with a high-fat atherogenic western-type diet (WD) for differing intervals over several weeks aimed at inducing various phases of NASH. In addition to the WD, the mice were treated with KU for 3 weeks or 4 months. Acute and chronic KU treatments were observed to be safe at the given concentrations with no toxicity indications in the mice. KU was found to alleviate NASH-related hepatotoxicity, mitochondrial and oxidative stress, and decrease the liver triglyceride content and TNF-α mRNA in at least one set of in vivo experiments. The KU modulated liver expression of selected metabolic and oxidative stress-related genes depended upon the length and severity of the disease. Although KU failed to completely reverse the histological progression of NASH in the mice, we demonstrated the complexity of mTORC1/C2 signaling regulation and suggest a stratified therapeutic management approach throughout the disease course.

The present investigation to decide the flavonoids isolated from Cadaba farinosa (Linn) has been screened for its antiatherogenic activity. We have isolated flavonoids by column chromatography on the methanolic extract of Cadaba farinosa. Flavonoids 1 from Cadaba farinosa were evaluated at a fixed dose of 15 mg/kg/day. The atherogenic diet (AD) is used to induce hyperlipidemia in wistar albino rats, and the plasma levels of various biochemical markers, including total cholesterol, triglycerides, LDL, VLDL, and HDL cholesterol, as well as invivo antioxidant enzymes like SOD and CAT, are then measured. 24 male Wister rats were distributed into the four groups of six rats each as follows: Standard chow diet was administered to group 1, an atherogenic diet was administered to group 2, Rats in groups 3 and 6 received atorvastatin (1.2 mg/kg B.wt.) and AD with flavonoids from Cadaba farinosa (15 mg/kg B.wt.). After an overnight fast, all rats were slaughtered at the end of three weeks via cervical dislocation. When compared to groups of rats treated with AD, the flavonoids (CF1) from Cadaba farinosa-administered rats had significantly lower body weight, plasma and tissue total cholesterol, TG, phospholipids, plasma Low density lipoprotein, and Very Low density lipoprotein, as well as higher plasma levels of HDL, SOD, and CAT. We came to the conclusion that the flavonoids (CF1) from Cadaba farinosa are a significant hypolipidemic agent with preventative and therapeutic activity against hyperlipidemia after considering the findings. [ABSTRACT FROM AUTHOR]

In the current study, we have evaluated the effect of gum Arabic on cholesterol homeostasis in atherogenic rats. To this end, adult male Wistar rats were treated orally with increasing concentrations of gum Arabic for 6 consecutive weeks, and serum concentrations of markers of cholesterol homeostasis (total cholesterol, low-density lipoprotein, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase activity) were evaluated. Treatment of atherogenic rats with gum Arabic improved serum levels of markers of cholesterol homeostasis. Also, gum Arabic did not reveal any harmful effect on the liver tissue of normal control rats, whereas the liver tissue of atherogenic-treated rats showed improvements in healing, inflammation, and necrosis. In conclusion, gum Arabic may serve to improve cholesterol homeostasis in patients with hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Introduction: Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis (AS), and involves a complex interplay between blood components, macrophages, and arterial wall. Therefore, it is valuable in the development of targeted therapies to treat AS. Methods: AS rat model was induced by atherogenic diet plus with lipopolysaccharide (LPS) and then treated by anti-malarial artesunate (Art), a succinate derivative of artemisinin. The arterial morphology was observed after Oil red O, hematoxylin--eosin, and Masson's staining. The arterial protein level was detected by immunohistochemistry or immunofluorescence. The expression level of mRNA was determined by PCR array or real-time PCR. Results: Herein, we showed that Art possessed a dose-dependently protective effect on AS rats. In detail, Art showed a comparable inhibitory effect on arterial plaque and serum lipids compared to those of rosuvastatin (RS), and further showed a better inhibition on arterial lipid deposition and arterial remodeling comprised of arterial wall thicken and vascular collagen deposition, than those of RS. The improvement of Art on AS rats was related to inhibit arterial macrophage recruitment, and inhibit nuclear factor κB (NF-κB)-related excessive arterial inflammatory responses. Critically, Art showed significant inhibition on the NLRP3 inflammasome activation in both arterial wall and arterial macrophages, by down-regulating the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and apoptosis associated speckle-like protein containing CARD (ASC), leading to less production of the NLRP3 inflammasome--derived caspase-1, interleukin-1β (IL-1β), IL-18, and subsequent transforming growth factor β1 (TGF-β1) in AS rats. Conclusion: We propose that Art is an anti-AS agent acts through modulating the arterial inflammatory responses via inhibiting the NF-κB - NLRP3 inflammasome pathway. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic steatohepatitis is the inflammatory subtype of nonalcoholic fatty liver disease with a high risk of progression to liver fibrosis. We investigated metabolic steatohepatitis with advanced liver fibrosis in apolipoprotein E/low‐density lipoprotein receptor double‐knockout (AL) mice fed a co‐diet of ethanol with a low‐carbohydrate–high‐protein‐high‐fat atherogenic diet (AD) for 16 weeks. We also examined the underlying mechanisms, especially hepatic sympathetic activation, involved in the effects. Methods: We maintained 12‐week‐old male AL mice on AD and a standard chow diet (SCD) with or without ethanol treatment for 16 weeks. Age‐matched male C57BL/6J mice on SCD without ethanol treatment served as controls. We conducted blood biochemical, histopathological, and fluorescence immunohistochemical, and reverse transcriptase polymerase chain reaction studies. Results: AL mice showed significant hyperlipidemia. AD induced increased body weight, hepatic steatosis, and hepatic damage; ethanol and the AD co‐diet resulted in hepatic sympathetic activation accompanied by hepatic steatosis, lobular inflammation, bridging fibrosis, and hepatic damage. Hepatic Kupffer cells (KCs) and hepatic stellate cells (HSCs), which showed sympathetic activation, produced 4.4‐ to 9.4‐fold more inflammatory factors (KC and KC‐derived tumor necrosis factor‐α, and chemokine [C‐C motif] ligand 2) and 2.0‐ to 32.0‐fold more fibrosis factors (HSC and HSC‐derived transforming growth factor β1 and collagen 1a1); all p < 0.05 vs. controls. Conclusions: We created a model of metabolic steatohepatitis with advanced liver fibrosis from coexisting hyperlipidemia and hepatic sympathetic activation in AL mice on a co‐diet of ethanol and AD. KCs and HSCs became the cellular targets of hepatic sympathetic activation, which could play a role in the initiation and progression of metabolic steatohepatitis with advanced liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: Curcumin (Cur) is a natural yellow polyphenol extracted from the turmeric rhizome (Curcuma longa). Cur is known for its potential therapeutic properties as an analgesic, anti-inflammatory, antioxidant, antimicrobial, hepatoprotective, and anti-mutagenic, although some of these biological activities remain unproven. Epidemiological studies have shown a positive relationship between high-fat diets and diet-related chronic diseases. We hypothesized that some adverse effects of consuming atherogenic or high-fat diets (AD) can be ameliorated by Cur supplementation. Using an experimental model of rats, this study investigated the significance of Cur when it is given as a supplement in an AD. Methods: Healthy adult Wistar rats were randomly assigned to one of three groups. Controls (C) received a standard diet and experimental rats were fed with AD or AD+Cur for 5 weeks. Cur (100 mg/kg body weight) was given orally daily, plus piperine (5 mg/kg body weight). The effect of Cur supplementation was studied on zoometrics, visceral fat content, serum lipids profile, hepatosteatosis, liver function and oxidative status. Results: Diets did not alter energy consumption. As compared to the other groups, AD+Cur group showed a lower total visceral fat content, percentage of perirenal, mesenteric, and pelvic fat, and body weight gain (P< 0.05). Serum total cholesterol (P<0.0001), non-HDL-C (P<0.0001) levels were significantly higher in AD groups as compared with C. Serum triglycerides and HDL-C levels remained similar among groups (P>0.05). AD induced a liver injury with macrovesicular steatosis and portal inflammation. AD+Cur rats presented microvesicular steatosis with no inflammation, achieving the lowest level of alanine aminotransferase (ALT; P<0.0001) and reductions of aspartate aminotransferase (AST; P<0.0001). Liver homogenates from AD+Cur showed that Cur supplementation reduced the dichlorofluorescein diacetate (DCFH-DA) oxidation rate induced by AD by 25 % and deferoxamine and superoxide dismutase inhibited DCFH-DA. Conclusion: Cur as a dietary supplement showed a protective effect against obesity and inflammation, but its cardioprotective ability remained unproved. Cur may develop as a promising therapeutic agent for liver diseases induced by oxidative stress. This study provides supporting evidence to confirm the beneficial effects of curcumin from the point of view of functional food science. [ABSTRACT FROM AUTHOR]

Objective(s): Hypercholesterolemia is a common metabolic disorder in developing and developed countries and is associated with the increased rates of chronic kidney disease (CKD). Statin therapy could reduce cholesterol synthesis as well as progression of CKD. Diversity between statins causes variety in pharmacokinetics and pharmacodynamics and also their pleiotropic effects. In the present investigation we aimed to evaluate the protective potentials of both atorvastatin (Ator) (as lipid-soluble statin) and rosuvastatin (Ros) (as water-soluble statin) against renal histopathological damages in the high cholesterol diet induced hypercholesterolemic rats (HCDIHR).Materials and Methods: Serum lipid profile, oxidized low density lipoprotein (OX-LDL), malondialdehyde (MDA), urea and creatinine levels, as well as renal histopathology were evaluated.Results: While Ros acted better than Ator to reduce serum low density lipoprotein cholesterol (LDL-C) (PConclusion: The findings underline that the lipophilic Ator may performs better than Ros in attenuating renal damages in HCDIHR.

Natural dietary supplements are progressively getting famous to supplant synthetic substances particularly in chronic morbidities. The aim of this study was to evaluate the anti-obesity potential of almond on the normal, Cafeteria, and Atherogenic diets. Parameters such as change in body weight, body temperature, lipid profile, organ weights, and fat pad weights were assessed. Central Nervous System related studies (Despair Swim test and Elevated Plus maze test) were also performed to comprehend the effect of the diets, and almond on the brain. All of the experimental animals were randomly assigned to one of three diet categoriesregular, cafeteria, or atherogenic, and fed those diets for 40 days. Each diet had the control group, standard drug group and three almond groups (low dose: 50; medium dose: 100 and high dose: 200 mg/kg body weight). Body weight was recorded every alternate day. On 40th day, body temperature was measured. On day 41, lipid parameters, organ weights, fat pad weights and the CNS parameters were evaluated. ANOVA followed by Duncans Multiple Range Test were used for statistical analysis. Treatment of animals with either a low or high dose of almond as well as a standard herb prevented a rise in body weight significantly (p = 0.01) in all three diet groups. When a regular diet was replaced with a cafeteria and atherogenic diet, the serum levels of triglycerides and LDL increased significantly, while HDL levels decreased significantly. Overall, almond preparation reduced lipid parameters, organ weights, fat-pad weights, and stabilized CNS parameters substantially. The almond high dose was the most effective of all the almond preparations. Our study suggests that chronic administration of almond independently reduces the body weight in experimental animals. [ABSTRACT FROM AUTHOR]

Background: Elevated inflammatory biomarkers in Metabolic Syndrome (MetS) are associated with Dietary Inflammatory Index (DII), which helps discern the inflammatory impacts of diet and hence the risk of Cardiovascular Diseases (CVD) in MetS. Aim and Objectives: To assess the association between DII scores and different components of MetS. To discern the degree of association between the dietary inflammatory potential and different components of MetS using the DII score specific to this population. Material and Methods: DII scores were calculated in 100 MetS participants and the diet was graded from maximally anti-inflammatory to maximally proinflammatory. Data were represented as mean ± standard deviation and compared using correlation coefficient and chi-square test. Results: DII scores were partially correlated with triglycerides (TG; P = 0.279) in the first quartile, with systolic blood pressure (P = 0.145) in the second, with High Density Cholesterol (HDL) in the third (P = - 0.0001), and with Triglycerides (TG) (P = 0.139) and diastolic blood pressure (P = 0.203) in the fourth quartile. Conclusion: The results reflect the role of diet in regulation of inflammation and are imperative to transform to a low inflammatory, antioxidant-rich diet to lower CVD risk.

Objective: To evaluate the anti-obesity activity of ethanolic extract of cashew apple using various in vitro and in vivo models. Methods: Phytochemical screening was carried out in ethanolic extract of cashew apple, followed by quantification of phenol and flavonoid. Antioxidant potential was evaluated using 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) scavenging assays. The inhibitory effect of ethanolic extract of cashew apple on α-amylase and pancreatic lipase was also studied. In addition, anti-obesity activity was determined in two in vivo models, lipid emulsion model and atherogenic diet-induced obese rat model. Levels of postprandial plasma triglycerides were assessed in lipid emulsion model, whereas serum lipid profile, in vivo antioxidants and histopathological studies of the carotid artery and liver were performed in an atherogenic diet-induced obese model. Results: Phytochemical screening revealed the presence of carbohydrates, alkaloids, polyphenols, terpenoids, and steroids. The in vitro assays showed inhibition of α-amylase and pancreatic lipase and strong antioxidant potential. Ethanolic extract of cashew apple showed significant and time- dependent inhibitory activity on postprandial triglycerides after administration of lipid emulsion for 5 h. Ethanolic extract of cashew apple at 200 and 400 mg/kg on day 60 showed a significant reduction in body weight, body mass index and atherogenic index, whereas lipid profile and liver function marker levels in the serum were decreased in a dose-dependent manner at time intervals (day 0, 20, 40, and 60) compared to the atherogenic diet-induced obese rats. Histological observations showed reduced non-alcoholic fatty liver deposits and decreased atherosclerotic fatty streak plaques (carotid artery) after treatment with ethanolic extract of cashew apple. Conclusions: Ethanolic extract of cashew apple ameliorates obesity, which may be partly mediated by its delayed absorption of cholesterol and carbohydrates.

Atherosclerosis is a vascular disease that is the main cause of hypercholesterolemia. Statins are the most effective cholesterol-lowering drugs to date and metformin is also thought to have anti-atherosclerotic effects in addition to hypoglycemic effects. Statin-associated muscle symptoms (SAMS) are the effect of statin use up to 72%. To determine the effectiveness of the combination of simvastatin and metformin following the atherogenic diet in male Wistar rats. All rats were divided into five experimental groups. The negative control group (n = 5), the positive control group were given the atherogenic diet alone (n = 5), the P1 group were treated with simvastatin 20 mg / BW / day (n = 5), the P2 group were treated with simvastatin 40 mg / BW / day (n = 5), the P3 group were treated with simvastatin 40 mg / BW / day and added with metformin 2 g/BW. All drugs were given after a two-week atherogenic diet. All groups of rats were measured for body weight and length before the diet, in the second week, and after four weeks. Before the rats were sacrificed, blood is drawn to be measured for cholesterol, creatinine, ALT, and AST. After four weeks, the animals were sacrificed and collected for the aorta, liver, and muscles of the right leg organ. All the organs were then measured for their weight. In the measurement of the aortic organ weight (P = 0.041), there was a significant difference in the results in each treatment group, while the examination of the weight of the liver (P = 0.077) and leg muscles (P = 0.831) was not a significant difference in each group. On cholesterol measurement, there was a significant difference (P = 0.000) in each treatment group, while there was no significant difference in creatinine (P = 0.052), ALT (P = 0.059), and AST (P = 0.824) levels. On body weight (P = 0.003), Body Mass Index (BMI) (P = 0.002) and Lee index (P = 0.002) measurement, there were significant differences after the diet in each group, while body length (P = 0.249) was not significantly different after diet in each group. Conclusion We conclude, there is an association between simvastatin and metformin combination administration in male Wistar rats after being given an atherogenic diet. [ABSTRACT FROM AUTHOR]

Background and Aim: This study was designed to determine the effects of a new atherogenic diet formulated at Institut Pertanian Bogor (IPB) (Bogor, Indonesia) on metabolic, morphometric, and carotid artery imaging of cynomolgus monkeys. Materials and Methods: A total of 20 adult male cynomolgus monkeys fed IPB-1 atherogenic diet for 1 year. Total plasma cholesterol (TPC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and morphometric measurements were evaluated at baseline and monthly during the study. Carotid plaques and intima-media thickness (IMT) were measured using ultrasonography at baseline and after 8 months of treatment. Results: This diet increased TPC, LDL, and TPC/HDL ratio and induced carotid atherosclerosis in this model. The TPC, LDL, and TPC/HDL ratio were positively associated; however, HDL was negatively associated with carotid plaques and IMT. Conclusion: The IPB-1 atherogenic diet formulated with locally and readily available ingredients provides an economically and scientifically feasible monkey model to study atherosclerosis in Indonesia and Southeast Asia.

Objective(s): Hypercholesterolemia is a common metabolic disorder in developing and developed countries and is associated with the increased rates of chronic kidney disease (CKD). Statin therapy could reduce cholesterol synthesis as well as progression of CKD. Diversity between statins causes variety in pharmacokinetics and pharmacodynamics and also their pleiotropic effects. In the present investigation we aimed to evaluate the protective potentials of both atorvastatin (Ator) (as lipidsoluble statin) and rosuvastatin (Ros) (as water-soluble statin) against renal histopathological damages in the high cholesterol diet induced hypercholesterolemic rats (HCDIHR). Materials and Methods: Serum lipid profile, oxidized low density lipoprotein (OX-LDL), malondialdehyde (MDA), urea and creatinine levels, as well as renal histopathology were evaluated. Results: While Ros acted better than Ator to reduce serum low density lipoprotein cholesterol (LDL-C) (P<0.01), atherogenic index (AI) (P<0.01), MDA (P<0.01), and OX-LDL (P<0.01); no significant differences were noted in their cholesterol (P=0.72), triglyceride (TG) (P=0.79), and very low density lipoprotein cholesterol lowering (VLDL-C) (P=0.79) and high density lipoprotein cholesterol elevating effects (HDL-C) (P=0.72). Ator was more effective to reduce renal histopathologic indices compared to Ros, including accumulation of lipid droplet, glomerular foam cells, mesangial cell proliferation, renal hemorrhage, and tubulointerstitial damages in the kidneys of diet induced hypercholesterolemic rats. Conclusion: The findings underline that the lipophilic Ator may performs better than Ros in attenuating renal damages in HCDIHR. [ABSTRACT FROM AUTHOR]

This study aimed to develop an improved and more reliable atherogenic diet-induced model of hyperlipidemia in Wistar rats for a better insight into pathophysiological changes and their effects on relevant biochemical and histological markers as well as on the thickness of the abdominal aorta. The study was conducted on a total number of 24 Wistar rats, three-month-old, weighing 180–230g that were divided into two groups: the standard rodent diet (SD) group (n = 12; 6 males and 6 females) in which rats were fed with commercially available standard rodent diet (SRD), and the atherogenic rodent diet (AD) group (n = 12; 6 males and 6 females) in which rats were fed with our mixture of atherogenic rodent diet (ARD) throughout the study period of 28 days. The body weight of rats was recorded weekly. The blood samples were collected by cardiac puncture and values of total cholesterol (TC) and triglycerides (TG) were determined at baseline, after the 14 days, and on the last day of the study, while other parameters high-density lipoprotein (HDL) cholesterol, lowdensity lipoprotein (LDL) cholesterol, non-HDL cholesterol, total protein (TP), glucose (GC), alanine transaminase (ALT), and aspartate transaminase (AST) were determined only on the last day of the study. The liver and abdominal aorta were collected after sacrifice and stored for further analysis. Feeding rats with an ARD for 14 days resulted in the successful development of hyperlipidemia, as the TC and TG values were significantly increased (p < 0.05). Further feeding with an ARD for a total of 28 days resulted in significantly increased levels of TC, TG, LDL, non-HDL, and decreased levels of HDL compared to rats fed with SRD (p < 0.05). Greater risk predispositions for CVDs were documented for rats in the AD group, due to the significant increase in AI and LDL/HDL ratio compared to the SD group (p < 0.05). Obtained lipid profile and predictors confirm the establishment of a diet-induced model of hyperlipidemia in Wistar rats and prove the suitability of our model for future testing and proving the effectiveness of lipid-lowering agents. [ABSTRACT FROM AUTHOR]

The anti-atherogenic activity of HDL is mainly due to their capacity to mediate reverse cholesterol transport (RCT). However, it is not clear to what extent this activity is affected by aging or pro-atherogenic conditions. Three and 24-month-old C57Bl/6 mice were fed an atherogenic diet (high fat, high cholesterol) for 12 weeks. The aged mice displayed a significant reduction in the capacity of HDL to mediate RCT (29.03%, p < 0.0006). Interestingly, the atherogenic diet significantly stimulated the RCT process in both young and aged mice (241% and 201%, respectively, p < 0.01). However, despite this, significant amounts of cholesterol accumulated in the aortas of mice fed an atherogenic diet as compared to regular chow. The accumulation of cholesterol was more marked in the aortas of aged mice (110% increase, p < 0.002). ABCA1 and ABCG1 protein expression on macrophages decreased significantly (52 to 37% reduction, p < 0.002), whereas their expression on hepatic cells increased significantly (up to 590% for ABCA1 and 116% for ABCG1, p < 0.002). On the other hand, SR-BI protein expression on hepatic cells decreased significantly (42.85%, p < 0.0001). ABCG5, ABCG8, and CYP7a protein expression on hepatic cells was also higher in mice fed an atherogenic diet. The increase was age-dependent for both ABCG5 and ABCG8. Our results suggest that the susceptibility to diet-induced atherosclerosis is exacerbated with aging and is a consequence of the dysregulation of the expression levels of membrane cholesterol transporters.

Background: Elevated inflammatory biomarkers in Metabolic Syndrome (MetS) are associated with Dietary Inflammatory Index (DII), which helps discern the inflammatory impacts of diet and hence the risk of Cardiovascular Diseases (CVD) in MetS. Aim and Objectives: To assess the association between DII scores and different components of MetS. To discern the degree of association between the dietary inflammatory potential and different components of MetS using the DII score specific to this population. Material and Methods: DII scores were calculated in 100 MetS participants and the diet was graded from maximally anti-inflammatory to maximally proinflammatory. Data were represented as mean ± standard deviation and compared using correlation coefficient and chi-square test. Results: DII scores were partially correlated with triglycerides (TG; P = 0.279) in the first quartile, with systolic blood pressure (P = 0.145) in the second, with High Density Cholesterol (HDL) in the third (P = - 0.0001), and with Triglycerides (TG) (P = 0.139) and diastolic blood pressure (P = 0.203) in the fourth quartile. Conclusion: The results reflect the role of diet in regulation of inflammation and are imperative to transform to a low inflammatory, antioxidant-rich diet to lower CVD risk. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the anti-obesity activity of ethanolic extract of cashew apple using various in vitro and in vivo models. Methods: Phytochemical screening was carried out in ethanolic extract of cashew apple, followed by quantification of phenol and flavonoid. Antioxidant potential was evaluated using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) scavenging assays. The inhibitory effect of ethanolic extract of cashew apple on α-amylase and pancreatic lipase was also studied. In addition, anti-obesity activity was determined in two in vivo models, lipid emulsion model and atherogenic diet-induced obese rat model. Levels of postprandial plasma triglycerides were assessed in lipid emulsion model, whereas serum lipid profile, in vivo antioxidants and histopathological studies of the carotid artery and liver were performed in an atherogenic diet-induced obese model. Results: Phytochemical screening revealed the presence of carbohydrates, alkaloids, polyphenols, terpenoids, and steroids. The in vitro assays showed inhibition of α-amylase and pancreatic lipase and strong antioxidant potential. Ethanolic extract of cashew apple showed significant and time- dependent inhibitory activity on postprandial triglycerides after administration of lipid emulsion for 5 h. Ethanolic extract of cashew apple at 200 and 400 mg/kg on day 60 showed a significant reduction in body weight, body mass index and atherogenic index, whereas lipid profile and liver function marker levels in the serum were decreased in a dose-dependent manner at time intervals (day 0, 20, 40, and 60) compared to the atherogenic diet-induced obese rats. Histological observations showed reduced non-alcoholic fatty liver deposits and decreased atherosclerotic fatty streak plaques (carotid artery) after treatment with ethanolic extract of cashew apple. Conclusions: Ethanolic extract of cashew apple ameliorates obesity, which may be partly mediated by its delayed absorption of cholesterol and carbohydrates. [ABSTRACT FROM AUTHOR]

The current study was conducted to investigate the physiological-protective effect of sage tea (Salvia officinalis L.) by their roles in controlling on lipid profile in laboratory male rats. In this study, 60 albino male laboratory rats (100-160 g) and aged (4-7 weeks) were used. The animals were randomly divided into three main groups (six rats per group) according to the experimental design of the study, the first group fed on a standard diet was considered as a control group and the group that fed on atherogenic diet for 28 days as a second group (A). While, the other group(B) (including sub groups), fed previously on atherogenic diet for 28 days were given orally administrated as following: The third group (B) include sub-groups (B1) and (B2) were given sage tea (S. officinalis) (0.086 mg/kg body weight) for 14 and 28 days respectively, The current study included the measurement of variations in body weight,andboth kidney function parameters (creatinine and urea) in serum. As well as, the histopathological study of kidney organ. The results of the study was showed a significant increase (p d” 0.05) in the body weight of rats that fed with high fat diet (HFD) (group A) when compared with the control group fed on a standard diet. While, the body weights in other groups were decreased in sage tea treated group (group B), The results of the kidney function tests showed a significant increase (p d” 0.05) of serum creatinine and urea levels in animals that fed on high fat diet (group A) when compared with control group. While, the serum levels of creatinine and serum urea were significantly decreased (p d” 0.05) and all treated groups with sage tea, (group B) respectively, for both periods 14 and 28 days. Besides that, the histopathological examinations of the current study revealed histological changes in the liver and kidney organs due to feeding on high fat diet (group A) compared with the control group. These changes including a congestion in the blood vessels, and steatosis in the kidney tissue. Whereas, the animals were treated with sage tea the photo microscopic examination of the kidney organ showed normal histological characters of less fat deposition and improvement in histo-structural features compared with animals group treated with atherogenic diet (group A). This indicate that improvement was associated with longterm treatment (28 days). Concludes from the current work, the administration of sage tea have an effective synergistic protective role on reducing the functional performance and normal histological characters of kidney organ that associated with long-term treatment (28 days). [ABSTRACT FROM AUTHOR]

The present work was designed to explore the functionality of Pakistani date cultivar (Zahidi) against atherogenic diet induced oxidative stress. The bioefficacy assessment of Zahidi date fruit and extract was carried out via model feeding trial. The rats (Sprague Dawley) were divided into two broad categories; one fed with normal diet, whereas the other was fed with atherogenic diet to induce oxidative stress. The formulated groups were G1 (normal diet), G2 (date fruit + normal diet), G3 (date extract + normal diet), G4 (atherogenic diet), G5 (date fruit + atherogenic diet) and G6 (date extract + atherogenic diet). The results showed that date fruit reduced 3.65% serum cholesterol in normal rats, and 15.14% in atherogenic rats, while, the date extract treatment resulted in 4.49 and 18.55% reduction in normal and atherogenic rats, respectively. Low-density lipoprotein (LDL) cholesterol reduced by 8.66 and 11.55% in date fruit and date extract fed normal rats, respectively, while 21.05 and 25.98% reductions were noted in the atherogenic groups fed with date fruit and date extract, respectively. To assess the extent of cardiac risk in the subjects, several atherogenic ratios were calculated based on the serum lipid parameters. The analysis showed that atherogenic diet groups were at higher risk than the normal ones, and that date fruit and extract containing functional diets effectively ameliorated the elevated risk ratios. The date fruit and extract-based diets intensified serum superoxide dismutase (SOD) and catalase (CAT) levels throughout the study up to 29.05 and 27.99%, respectively. Date fruit effectively lowered lipid peroxidation by 13.64 and 33.67% in normal and atherogenic rats, respectively. Conclusively, date fruit and extract treatment proved effectual in modulating the serum lipid profile and effectively restored the SOD and CAT levels alongside reducing the lipid peroxidation. [ABSTRACT FROM AUTHOR]

Antioxidant and antihyperlipidemic actions of Glycyrrhiza glabra roots for aqueous and ethanolic extracts were examined by studying its in vitro inhibitory effect on lipid peroxidation and in vivo effects on atherogenic diet (2% cholesterol, 1% Choline Chloride and 2% Lard) induced rats hyperlipidemia. In cholesterol induced hyperlipidemic model, groups of rats treated with extracts G.glabra showed a significant reduction in total cholesterol (TC), triglycerides (TG), atherogenic index , SGOT, SGPT and ALP activities whereas increase in the level of high density lipoprotein (HDL)compared to cholesterol induced hyperlipidemic control group at dose dependent manner but the effect was less than the standard drug Atorvastatin. It was also identified from the histopathological results that rats fed with G.glabra extracts exposed decrease in granular degeneration caused by cholesterol feedings. [ABSTRACT FROM AUTHOR]

Antioxidant and antihyperlipidemic actions of Glycyrrhiza glabra roots for aqueous and ethanolic extracts were examined by studying its in vitro inhibitory effect on lipid peroxidation and in vivo effects on atherogenic diet (2% cholesterol, 1% Choline Chloride and 2% Lard) induced rats hyperlipidemia. In cholesterol induced hyperlipidemic model, groups of rats treated with extracts G.glabra showed a significant reduction in total cholesterol (TC), triglycerides (TG), atherogenic index, SGOT, SGPT and ALP activities whereas increase in the level of high density lipoprotein (HDL)compared to cholesterol induced hyperlipidemic control group at dose dependent manner but the effect was less than the standard drug Atorvastatin. It was also identified from the histopathological results that rats fed with G.glabra extracts exposed decrease in granular degeneration caused by cholesterol feedings. [ABSTRACT FROM AUTHOR]

The activation of two transcription factors, NFκB and NICD (notch intracellular domain), plays a crucial role in different stages of atherosclerotic disease progression, from early endothelial activation by modified lipids like oxidized low‐density lipoprotein (oxyLDL) to the imminent rupture of the atherosclerotic plaque. Inflammatory mediators and the notch pathway proteins were upregulated in atherogenic diet‐induced rats and the same was confirmed by the differentiation of monocyte to macrophage on exposure to oxyLDL. The inflammatory transcription factor NFκB and the notch signaling transcription factor NICD were analysed for their molecular interaction in monocyte to macrophage differentiation. Inhibition of NFκB by dexamethasone in monocyte to macrophage differentiation resulted in a concomitant downregulation of NICD, whereas inhibition of NICD by N‐(N‐[3, 5‐difluorophenacetyl])‐l‐alanyl)‐S‐phenylglycine t‐butyl ester (DAPT), a γ–secretase inhibitor, did not significantly influence the expression of NFκB, but downregulated macrophage differentiation. These findings revealed that NFκB inhibition using dexamethasone regulated NICD, which turned down macrophage differentiation. Thus, inhibition of both NFκB–NICD is a potential target for intervention in atherosclerosis. Inhibition of NFκB regulated notch intracellular domain (NICD), which, in turn, downturned macrophage differentiation. Inhibition of both NFκB–NICD is a potential target for intervention in early stage of atherosclerosis (monocyte to macrophage differentiation), to prevent the furtherance of disease. [ABSTRACT FROM AUTHOR]

Background: Alcohol abuse and adherence to atherogenic diet (AD; a low‐carbohydrate–high‐protein diet) have been positively associated with cardiovascular disease. In addition, it has been demonstrated clinically that dietary intake is increased on days when alcohol is consumed. Here, the additive effects of ethanol (EtOH) and AD on atherosclerosis, a major underlying cause of cardiovascular disease, were investigated in apolipoprotein E/low‐density lipoprotein receptor double‐knockout (KO) mice. The mechanisms, especially aortic oxidative stress damage, were highlighted. Methods: Twelve‐week‐old male KO mice on AD with or without EtOH treatment were bred for 4 months. Age‐matched male C57BL/6J mice on a standard chow diet without EtOH treatment served as controls. Analyses were conducted using ultrasound biomicroscopy, histopathological and fluorescence immunohistochemical examinations, Western blots, and polymerase chain reaction. Results: KO mice on AD with EtOH treatment showed increases in aortic maximum intima media thickness, hypoechoic plaque formation, and mean Oil‐Red‐O content. These results were associated with enhanced ratio of aortic 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG)‐immunopositive area to the metallothionein (MT) immunopositive area and suppression of AD‐induced up‐regulated aortic Mt1, Mt2, and upstream stimulatory factor 1 mRNA expressions. Moreover, 8‐OHdG was expressed in the nuclei of CD31‐ and alpha smooth muscle actin‐immunopositive cells, and the up‐regulated mRNA expressions of aortic nitric oxide synthase 3 and platelet‐derived growth factors were only observed in the KO mice on AD with EtOH treatment. Conclusions: Alcohol abuse and adherence to AD may promote the shift of aortic oxidative stress and antioxidative stress balance toward oxidative stress predominance and reduced antioxidative stress, which may be partly due to the decrease in MT at the cell biological level and down‐regulation of Mt at the gene level, which in turn could play a role in the up‐regulation of endothelial dysfunction‐related and vascular smooth muscle cell proliferation‐related gene expression and the progression of atherosclerosis in mice with hyperlipidemia. Alcohol consumption in combination with atherogenic diet increased indices of atherosclerosis in apolipoprotein E/low‐density lipoprotein receptor double‐knockout mice (A‐C) via promoting the shift of aortic oxidative stress and anti‐oxidative stress balance toward oxidative‐stress predominance and reduced anti‐oxidative stress (D‐G). Yellow arrowheads in C indicate hypoechoic plaque formations, 8‐OHdG and Cybb were used as oxidative stress markers and metallothionein (MT) was used as the anti‐oxidative stress marker. The data are presented as the means ± SDs. *p < 0.05. [ABSTRACT FROM AUTHOR]

Knowledge of the benefits of mTOR inhibition concerning adipogenesis and inflammation has recently encouraged the investigation of a new generation of mTOR inhibitors for non-alcoholic steatohepatitis (NASH). We investigated whether treatment with a specific mTORC1/C2 inhibitor (Ku-0063794; KU) exerted any beneficial impacts on experimentally-induced NASH in vitro and in vivo. The results indicated that KU decreases palmitic acid-induced lipotoxicity in cultivated primary hepatocytes, thus emerging as a successful candidate for testing in an in vivo NASH dietary model, which adopted the intraperitoneal KU dosing route rather than oral application due to its significantly greater bioavailability in mice. The pharmacodynamics experiments commenced with the feeding of male C57BL/6 mice with a high-fat atherogenic western-type diet (WD) for differing intervals over several weeks aimed at inducing various phases of NASH. In addition to the WD, the mice were treated with KU for 3 weeks or 4 months. Acute and chronic KU treatments were observed to be safe at the given concentrations with no toxicity indications in the mice. KU was found to alleviate NASH-related hepatotoxicity, mitochondrial and oxidative stress, and decrease the liver triglyceride content and TNF-α mRNA in at least one set of in vivo experiments. The KU modulated liver expression of selected metabolic and oxidative stress-related genes depended upon the length and severity of the disease. Although KU failed to completely reverse the histological progression of NASH in the mice, we demonstrated the complexity of mTORC1/C2 signaling regulation and suggest a stratified therapeutic management approach throughout the disease course. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease, stroke, atherosclerosis and hyperlipidemia are primary causes of death worldwide. Moringa Oleifera tree was used as a health supplement introduced to Africa from India. Its leaves have various biological activities, including hypolipidemic effect. Objective(s): The aim of present study was to assess the effect of Moringa Oleifera consumption on lipid profile and histopathology of the liver in hyperlipidemic rats. Methods: A total of 50 male albino rats were divided into five equal groups. Group I was left as control and fed on standard diet only. Group II was fed on standard diet and orally injected with 400 mg/kg of rat body weight extract of Moringa Oleifera. Hyperlipidemia was induced in the remaining 30 rats by feeding an atherogenic diet for four weeks. Group III was fed on atherogenic diet only. Group IV was fed on atherogenic diet and orally injected with 400 mg/kg of rat body weight extract of Moringa Oleifera. Group V was fed on atherogenic diet with 2mg/kg of rat body weight Atorvastatin drug. Lipid profile of rat blood was measured including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), and very low density lipoprotein (VLDL). Liver tissue was evaluated by carrying out histopathological examination. Results: The rats fed on Moringa Oleifera showed a significant decrease in total cholesterol and LDL by 26.8% and 40.6% respectively compared to baseline values after 4 weeks. Although VLDL and TG showed slight increase by 5.6% and 5.1% respectively, they were still within the normal range. Otherwise, there was a significant increase in LDL, VLDL, TC, and total TG levels in rats fed on atherogenic diet only by 17.13%, 195.4%, 29.2%, and 193% respectively compared to baseline values after 4 weeks. Atorvastatin drug affected the HDL level, as it increased by 16.4% % 28% from baseline after two and four weeks respectively. Atorvastatin and Moringa Oleifera decreased VLDL level by 53.9% & 36.5% respectively when compared to rats fed on atherogenic diet. Conclusion: Moringa Oleifera was comparable to hypolipidemic medication (Atorvastatin) in improving the lipid profile of rats fed on atherogenic diet. Moringa Oleifera intake is more effective in prevention than in treatment of hyperlipidemia.

Notch signaling plays a pivotal role in homeostasis and cardiovascular development. The role of notch signaling in atherosclerosis cannot be complete without analysing the key role of notch in macrophages, which trigger the inflammatory response and subsequent plaque formation in atherosclerosis. Diosgenin showed its anti-atherosclerotic property by the unifying mechanism of suppressing the expression of notch signaling pathway, particularly the nuclear translocation of notch intracellular domain (NICD) in aorta and in differentiated macrophage cells. It is further confirmed by the inhibition of NICD by DAPT (N-[N-(3, 5-difluorophenacetyl)- l -alanyl]-S-phenylglycine t -butyl ester), which also restricted the differentiation of macrophage. Hence, inhibition of nuclear translocation of NICD by diosgenin aids in preventing atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherogenic Diet (AD) was given to rats to understand the key role of inflammatory mediators in atherosclerotic lesion formation, as a serendipitous study, the diet induced inflammatory mediators in liver and brain, whereas pancreas, kidney and spleen were not affected. The efficacy of diosgenin in ameliorating atherosclerotic progression in heart and suppression of inflammatory mediators in liver and brain of Wistar rat fed on AD diet was investigated. Atherogenic diet triggered inflammatory mediators in heart, liver and brain by upregulating TNF-α, COX-2 and NFkBp65 which are the inflammatory hub, played a key role in pathophysiologic conditions. Endothelial dysfunction, liver tissue with prominent steatosis and the stress evoked in the brain by the atherogenic diet triggered these inflammatory mediators. TNF-α and COX-2 expression was upregulated and its elevation was associated with NFkBp65 activation in heart, liver and brain of atherogenic diet induced rat. Diosgenin downregulated these inflammatory mediators, thereby prevented the atherosclerotic disease progression and concomitant suppression of inflammatory mediators in liver and brain. [ABSTRACT FROM AUTHOR]

Background and Aims: Atherosclerosis has become a prominent health problem in Indonesia. Based on food as medicine concept, tempe gembus (a fermented food from Indonesia) is well known having the content of nutrient that influences atherosclerosis parameter. Research aimed to prove the influence of different variation of tempe gembus that was given without additional treatment (X1), with the steam blanching heating (X2), and was added the bromelain enzyme (X3) to the level of serum Homocysteine (Hcy) and Malondialdehyde (MDA)of rat's blood that was given the atherogenic diet. Material and Methods: The research of posttest randomized controlled group design on 35 Sprague dawley rats were divided into two main groups as follow; they were 2 control groups (called K- and K+) and 3 treatment groups. All of the treatment groups were given tempe gembus of 25 gram/kg rat body weight. Results: The results showed that group variation of tempe gembus had a lower mean of Hcy and MDA levels than disease group (K+). However, a significant effect of tempe gembus was only decrease in MDA level (ANOVA test p = 0.001). Treatment X1 and X3 had meaningful differences to decrease MDA levels. Conclusion: Tempe gembus variation can decrease the MDA level significantly and decrease the Hcy level however, without statistical significance. [ABSTRACT FROM AUTHOR]

Objective Atherogenic diet (AD) and high fat diet (HFD) cause deleterious effect on bone micro-architecture and this phenomenon prompts aortic calcification. This study aims to show the effects of Caviunin β- d -glucopyranoside (CAFG), against bone loss and its associated aortic calcification in presence of AD and HFD challenged diets. Methods Five groups of C57BL/6 male mice with 8 animals in each group, comprising of chow, AD, HFD, AD + CAFG and HFD + CAFG were fed with respective diets for 16 weeks. At the end of the treatment period, preventive effects of CAFG on bone tissue were analyzed by assessing the osteogenic potential of bone marrow cells, bone micro-architecture, ability of new bone formation and histomorphometry studies. Aortic calcification was assessed by transcription and translation analysis of osteogenic key markers in aortic tissue and assessment of aortic endothelial function. Plasma lipid profiling was done to assess the effects of diets as its role in both bone loss and aortic calcification. Results Bone marrow stromal cell (BMSC’s) dynamics showed that AD and HFD decreased osteoblast number that led to bone loss, deterioration in bone micro-architecture with up-regulated bone resorptive genes that lead to increase in aortic calcification. CAFG treatment rescued the bone health by modulating BMSC’s towards osteogenic lineage. It increased the osteogenic gene expression with simultaneous decrease in osteoclastic genes thus stabilized the receptor activator of nuclear factor-kappa-B ligand/osteoprotegerin ratio that eventually reduced the amount of calcification in aorta. Biochemical studies showed that CAFG reduced the TC, TG and LDL-C content with no marked changes in HDL-C. Moreover, CAFG decreased the osteogenic key markers in the aortic tissue and enhanced endothelial function. Conclusion Overall, this study indicates that CAFG protected against physiologically challenged diet induced bone loss with associated vascular calcification in mice. Moreover, data revealed that atherogenic diet is more detrimental as compared to the excess fatty acid diet to the bone and aorta. [ABSTRACT FROM AUTHOR]

Objective: To explore the effects of high cholesterol/high fat diet-induced hypercholesterolemia on pulmonary homeostasis of wild-type C57BL/6J mice. Materials and methods: Six- to eight-week-old male C57BL/6J mice were randomly divided into two groups and treated with either high cholesterol/high fat diet (HCD, containing 20 % fat, 1.25 % cholesterol and 0.5 % sodium cholate) or a matching regular diet (RD, containing 4 % fat with no cholesterol and cholate added) for 12-16 weeks. Results: Twelve to sixteen weeks after HCD diet feeding, hypercholesterolemia and pulmonary lipid accumulation were progressively exacerbated in C57BL/6J mice. Meanwhile, the HCD-fed mice showed distinctive signs of inflammation in the lung, which includes macrophage accumulation in alveolar lumen and lymphocyte infiltration around perivascular area. Simultaneously, the mRNA and protein expression of TLR2 and TLR4 were significantly up-regulated, and the translocation of NFκB into nucleus was activated in HCD-fed mice lung. In vitro, oxidized low-density lipoprotein (oxLDL) could directly up-regulate the expression of TLR2 and TLR4 in both A549 and MLE-12 lung epithelial cell lines. Conclusions: These findings suggested that high cholesterol/high fat diet-induced hypercholesterolemia could result in TLRs/NFκB pathway-associated low-grade pulmonary inflammation in C57BL/6J mice, which might alter the lung's immune responsiveness to a variety of environmental exposures. [ABSTRACT FROM AUTHOR]