Cardiovascular disease, in particular coronary artery disease (CAD), remains the most important cause of morbidity and mortality in developed countries and, in the near future, more so in the developing world. Atherosclerotic plaque formation is the underlying basis for CAD. Growth of the plaque leads to coronary stenosis, causing a progressive decrease in blood flow that results in angina pectoris. Acute myocardial infarction and unstable angina were recently recognised as related to plaque rupture, not progressive coronary stenosis. Acute thrombus formation causes an abrupt coronary occlusion. The characteristics of the fibrin cap, contents of the plaque, rheological factors and active inflammation within the plaque contribute to plaque rupture. Oxidative processes are important in plaque formation. Oxidized low density lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal macrophages, transforming them into foam cells which develop into fatty streaks, the precursors of the atherosclerotic plaque. Inflammation is important both in plaque formation and rupture. Animal studies have shown that antioxidants reduce plaque formation and lead to plaque stabilisation. In humans, high intakes of antioxidants are associated with lower incidence of CAD, despite high serum cholesterol levels. This observation suggests a role for inflammation in CAD and that reducing inflammation using antioxidants may ameliorate these processes. Men and women with high intakes of vitamin E were found to have less CAD. Vitamin E supplementation was associated with a significant reduction in myocardial infarction and cardiovascular events in the incidence of recurrent myocardial infarction. In the hierarchy of evidence in evidence-based medicine, data from large placebo-controlled clinical trials is considered necessary. Results from various mega-trials have not shown benefits (nor adverse effects) conferred by vitamin E supplementation, suggesting that vitamin E has no role in the treatment of CAD. These results do not seem to confirm, at the clinical level, the effect of antioxidants against active inflammation during plaque rupture. However, a closer examination of these studies showed a number of limitations, rendering them inconclusive in addressing the role of vitamin E in CAD prevention and treatment. Further studies that specifically address the issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment of CAD need be performed. These studies should use the more potent antioxidant property of alpha-tocotrienol vitamin E.
The present study aims to examine the effects of a palm-oil-derived vitamin E mixture containing tocotrienol (approximately 70%) and tocopherol (approximately 30%) on plasma lipids and on the formation of atherosclerotic plaques in rabbits given a 2% cholesterol diet. Eighteen New Zealand White rabbits (2.2-2.8 kg) were divided into three groups; group 1 (control) was fed a normal diet, group 2 (AT) was fed a 2% cholesterol diet and group 3 (PV) was fed a 2% cholesterol diet with oral palm vitamin E (60 mg/kg body weight) given daily for 10 weeks. There were no differences in the total cholesterol and triacylglycerol levels between the AT and PV groups. The PV group had a significantly higher concentrations of HDL-c and a lower TC/HDL-c ratio compared to the AT group (P < 0.003). The aortic tissue content of cholesterol and atherosclerotic lesions were comparable in both the AT and PV groups. However, the PV group had a lower content of plasma and aortic tissue malondialdehyde (P < 0.005). Our findings suggest that despite a highly atherogenic diet, palm vitamin E improved some important plasma lipid parameters, reduced lipid peroxidation but did not have an effect on the atherosclerotic plaque formation.
Paradoxically, meta-analysis of human randomized controlled trials revealed that natural but not synthetic α-tocopherol supplementation significantly increases all-cause mortality at 95% confidence interval. The root cause was that natural α-tocopherol supplementation significantly depressed bioavailability of other forms of vitamin E that have better chemo-prevention capability. Meta-analysis outcome demonstrated flaws in the understanding of vitamin E. Reinterpretation of reported data provides plausible explanations to several important observations. While α-tocopherol is almost exclusively secreted in chylomicrons, enterocytes secrete tocotrienols in both chylomicrons and small high-density lipoproteins. Vitamin E secreted in chylomicrons is discriminately repacked by α-tocopherol transfer protein into nascent very low-density lipoproteins in the liver. Circulating very low-density lipoproteins undergo delipidation to form intermediate-density lipoproteins and low-density lipoproteins. Uptake of vitamin E in intermediate-density lipoproteins and low-density lipoproteins takes place at various tissues via low-density lipoproteins receptor-mediated endocytosis. Small high-density lipoproteins can deliver tocotrienols upon maturation to peripheral tissues independent of α-tocopherol transfer protein action, and uptake of vitamin E takes place at selective tissues by scavenger receptor-mediated direct vitamin E uptake. Dual absorption pathways for tocotrienols are consistent with human and animal studies. α-Tocopherol depresses the bioavailability of α-tocotrienol and has antagonistic effect on tocotrienols in chemo-prevention against degenerative diseases. Therefore, it is an undesirable component for chemo-prevention. Future research directions should be focused on tocotrienols, preferably free from α-tocopherol, for optimum chemo-prevention and benefits to mankind.
Oxidative stress and reactive oxygen species (ROS) constitute a major pathogenic mechanism
for the development of atherosclerosis. In the present work, the antioxidant potential of
Trihoney was investigated in hypercholesterolaemic rabbits. Thirty-six male New Zealand
white (NZW) rabbits were grouped into: normal diet (C), normal diet with 0.6 g/kg/day of
Trihoney (C+H), 1% cholesterol diet (HCD), 1% cholesterol diet with 0.3 g/kg/day of
Trihoney (HCD+H1
), 1% cholesterol diet with 0.6 g/kg/day of Trihoney (HCD+H2
), and 1%
cholesterol diet with 2 mg/kg/day of atorvastatin (HCD+At.). Animals were sacrificed following 12 weeks of treatment, and their serum was analysed for oxidised-low density lipoprotein
(Ox-LDL). Serum and aortic tissue homogenate were assayed for superoxide dismutase
(SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Hypercholesterolemia
caused a significant (p < 0.05) elevation in serum Ox-LDL and a significant (p < 0.05) reduction of antioxidant enzyme activities in serum of the HCD group. Trihoney induced a significant (p < 0.05) increase in antioxidant enzyme activities in serum as compared to the HCD
group. The high cholesterol diet suppressed both antioxidant enzymes in aortic homogenate.
Trihoney significantly (p < 0.05) enhanced both antioxidant enzymes in aortic homogenate.
Hypercholesterolemia induced a significant (p < 0.05) elevation of serum lipid peroxidation in
the HCD group. Trihoney caused a significant (p < 0.05) reduction of lipid peroxidation in
aortic homogenate. These results demonstrated that Trihoney has the potential to ameliorate
oxidative stress systemically, as well as locally in the atherosclerotic aorta.
Germinated brown rice (GBR) is rich in bioactive compounds, which confer GBR with many functional properties. Evidence of its hypocholesterolemic effects is emerging, but the exact mechanisms of action and bioactive compounds involved have not been fully documented. Using type 2 diabetic rats, we studied the effects of white rice, GBR, and brown rice (BR) on lipid profile and on the regulation of selected genes involved in cholesterol metabolism. Our results showed that the upregulation of apolipoprotein A1 and low-density lipoprotein receptor genes was involved in the hypocholesterolemic effects of GBR. Additionally, in vitro studies using HEPG2 cells showed that acylated steryl glycoside, gamma amino butyric acid, and oryzanol and phenolic extracts of GBR contribute to the nutrigenomic regulation of these genes. Transcriptional and nontranscriptional mechanisms are likely involved in the overall hypocholesterolemic effects of GBR suggesting that it may have an impact on the prevention and/or management of hypercholesterolemia due to a wide variety of metabolic perturbations. However, there is need to conduct long-term clinical trials to determine the clinical relevance of the hypocholesterolemic effects of GBR determined through animal studies.
ABSTRACTAn energy-deficit (ED) diet increases lipid mobilisation, while endurance exercise improves lipid profile by promoting formation of high-density lipoproteins (HDLs) among moderately active population. However, it is not clear whether ED with high-intensity exercise training can improve lipid profiles. Therefore, 20 recreationally active males (20.3 ± 2.7 years old with peak oxygen consumption (
V
˙
O2peak) of 2.8 ± 0.2 L min-1) with HDL concentration of 1.44 ± 0.32 mmol L-1, were evenly allocated to either an ED group (1590 ± 79 kcal day-1: 40% of total caloric omitted at lunchtime) or a control (CON) group (2570 ± 139 kcal day-1). Participants in both groups performed high-intensity cycling at 90%
V
˙
O2peak at a constant workload for 8 min, 2 h after breakfast on day D0, D2, D4, D6, D8 and D10 (Dn is day number), after which blood samples were collected. In ED, compared to D0, triglycerides (TG) decreased on D6-10 (p LDL), total cholesterol (TC) increased on D2-10, while HDL progressively increased on D6-10 (p = .01) with a final value of 1.67 ± 0.24 mmol L-1. In CON, there were no changes in TG, TC and HDL while LDL was reduced on D8-10 (p = .01). Moreover, the proportions of TC/HDL and LDL/HDL increased in ED on D2-10 and D2-8 (p = .05), respectively, while LDL/HDL in CON was reduced on D8-10 (p = .01). In brief, 10 days of ED and a series of high-intensity exercise sessions show progressive elevation of HDL which suggest longer period is required to observe changes in lipid ratios.
An herbal mixture composed of lemon, apple cider, garlic, ginger and honey as a polyphenol-rich mixture (PRM) has been reported to contain hypolipidemic activity on human subjects and hyperlipidemic rats. However, the therapeutic effects of PRM on metabolites are not clearly understood. Therefore, this study aimed to provide new information on the causal impact of PRM on the endogenous metabolites, pathways and serum biochemistry. Serum samples of hyperlipidemic rats treated with PRM were subjected to biochemistry (lipid and liver profile) and hydroxymethylglutaryl-CoA enzyme reductase (HMG-CoA reductase) analyses. In contrast, the urine samples were subjected to urine metabolomics using 1H NMR. The serum biochemistry revealed that PRM at 500 mg/kg (PRM-H) managed to lower the total cholesterol level and low-density lipoprotein (LDL-C) (p < 0.05) and reduce the HMG-CoA reductase activity. The pathway analysis from urine metabolomics reveals that PRM-H altered 17 pathways, with the TCA cycle having the highest impact (0.26). Results also showed the relationship between the serum biochemistry of LDL-C and HMG-CoA reductase and urine metabolites (trimethylamine-N-oxide, dimethylglycine, allantoin and succinate). The study's findings demonstrated the potential of PRM at 500 mg/kg as an anti-hyperlipidemic by altering the TCA cycle, inhibiting HMG-CoA reductase and lowering the LDL-C in high cholesterol rats.
Diabetes mellitus or type-2 diabetes, commonly referred as diabetes, is a metabolic disorder that results in high blood sugar level. Despite the availability of several antidiabetic drugs in the market, they still do not adequately regulate blood sugar levels. Thus, in general people prefer to use herbal supplements/medicines along with antidiabetic drugs to control blood sugar levels. One of such herbal medicine is Swietenia macrophylla seeds. It is widely used in Asia for controlling blood sugar levels. One of the major bioactive compounds, Swietenine, is reported to be responsible for controlling blood glucose levels. However, there were no studies on its efficacy in controlling the blood glucose in diabetic rats. In this study, we evaluated the antihyperglycemic activity of Swietenine and its pharmacodynamic interaction with Metformin in Streptozotocin induced diabetes in rats. The activity of Swietenine was investigated at three different doses: 10, 20 and 40 mg/kg body weight (bw). Metformin (50 mg/kg bw) was used as a standard drug. Swietenine (20 and 40 mg/kg bw) and Metformin (50 mg/kg bw) showed significant effect in reducing the glucose, cholesterol, triglycerides, low-density lipoprotein, urea, creatinine, alanine transaminase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and malondialdehyde level in serum while it had increased the high-density lipoprotein, glutathione, and total antioxidant capacity level. In addition, Swietenine (20 and 40 mg/kg) had shown significant synergistic effect with Metformin. Administration of Swietenine at 10 mg/kg bw neither showed activity nor influenced Metformin's activity. The results from this study confirmed the beneficial effects of Swietenine and its synergistic action with Metformin in controlling the dysregulated serum parameters in Streptozotocin induced diabetes in rats.
The aim of this study was to investigate the responses of atherosclerosis plaque biomarkers to purslane seed consumption and aerobic training in women with T2D. 196 women with T2D were assigned into; (1) placebo (PL), (2) aerobic training+placebo (AT + PL), 3) purslane seeds (PS), aerobic training+purslane seeds (AT + PS). The training program and purslane seeds consumption (2.5 g lunch and 5 g dinner) were carried out for 16 weeks. The components of purslane seed were identified and quantified by GC-MS. Blood samples were withdrawn via venipuncture to examine blood glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, triglycerides (TG), creatinine, urea, uric acid, NF-κB, GLP1, GLP1R, TIMP-1, MMP2, MMP9, CRP, CST3, and CTSS expressions. Blood glucose, LDL, cholesterol, TG, creatinine, urea, and uric acid levels in the (P), (AT), and (AT + PS) groups were significantly decreased compared to the pre-experimental levels or the placebo group, while HDL, significantly increased. Furthermore, the protein and mRNA levels of NF-κB, TIMP-1, MMP2 &9, CRP, CST3, and CTSS in the (P), (AT), (AT + PS) significantly decreased compared to pre-experimental or the placebo group, while level of GLP1 and GLP1-R increased drastically. Findings suggest that purslane seed consumption alongside exercising could improve atherosclerosis plaque biomarkers through synergistically mechanisms in T2D.
This study evaluated the in vitro antioxidant capacities of extracts from Pleurotus pulmonarius via Folin-Ciocalteu, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging, metal chelating, cupric ion reducing antioxidant capacity, and lipid peroxidation inhibition assays. Extract compositions were determined by phenol-sulfuric acid; Coomassie Plus (Bradford) protein; Spectroquant zinc, copper, and manganese test assays; and liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-mass spectrometry (GC/MS). Methanol-dichloromethane extract, water fraction, hot water, aqueous extract and hexane fraction exhibited the most potent extracts in the antioxidant activities. LC/MS/MS and GC/MS showed that the extracts contained ergothioneine, ergosterol, flavonoid, and phenolic compounds. The selected potent extracts were evaluated for their inhibitory effect against oxidation of human low-density lipoproteins and protective effects against hydrogen peroxide-induced cytotoxic injury in human aortic endothelial cells. The crude aqueous extract was deemed most potent for the prevention of human low-density lipoprotein oxidation and endothelial membrane damage. Ergothioneine might be the compound responsible for the activities, as supported by previous reports. Thus, P. pulmonarius may be a valuable antioxidant ingredient in functional foods or nutraceuticals.
Oxidized low density lipoprotein plays an important role in development of foam cells in atherosclerosis. The study was focused on regulation of primary human monocyte growth and CD11b expression in presence of Nigella sativa oil.
The polyphenolic profiles and antioxidant activities of the water extracts of Barringtonia racemosa shoots (leaves and stems) were explored. Two methods, freeze drying and air drying, for preparation of the shoots, were also compared. Freeze drying was better as air drying caused 5-41% reduction of polyphenols. Three phenolic acids and three flavonoids were identified, using UHPLC. The descending order of polyphenols in the leaves and stems was gallic acid>ellagic acid>quercetin>protocatechuic acid>rutin>kaempferol. In vitro antioxidant analyses were performed using biological samples. In the LDL oxidation assay, B. racemosa leaf extract (IC50=73.0μg/ml) was better than stem extract (IC50=226μg/ml) at inhibiting the formation of TBARS and lipid hydroperoxides. Similar trends were observed for serum and haemoglobin oxidation. B. racemosa leaf extract was better than its stem extract in delaying the time required to oxidise haemoglobin to methaemoglobin. The high polyphenolic content of B. racemosa shoots could have contributed towards their antioxidative effects.
Plant-based polyphenolic compounds have been reported to possess cardiovascular health benefits. Several dietary sources, including herbs and spices, fruits and vegetables, and tea and wine, contain an array of biologically active compounds that have been shown to be effective in retarding oxidation of low-density lipoproteins (LDL) and promoting vascular relaxation. In the present study four different plant sources, both edible and non-edible, were evaluated for potential activity. Organic extracts enriched in polyphenols were prepared from palm fronds (Elaesis guineensis); lemongrass (Cymbopogon citrates); papaya shoots (Carica papaya) and green chilli (Capsicum frutescenes) and tested for their ability to prevent in vitro oxidation of LDL, and for potential vascular relaxation actions. Rings of rat thoracic aorta and isolated perfused mesenteric vascular beds were mounted in organ baths, contracted using a half-maximal dose of noradrenaline and exposed to cumulative additions of test extracts. Palm frond extract resulted in considerable relaxation (>75%) in both preparations and was found to be endothelium-dependent as removal of endothelium or inhibition of endogenous nitric oxide (NO) led to a total loss in relaxant activity. Lemongrass extract caused a greater relaxation action in the mesenteric preparation compared to aortic rings, and appears to be mediated via NO-independent and non-prostanoid mechanisms. Of the extracts tested, palm fronds also demonstrated the highest antioxidant capacity, as determined by the ferric reducing activity/potential assay, and resulted in a significant delay (P < 0.05) in the oxidation of LDL. Collectively, these preliminary findings lend further support to the potential cardiovascular actions of plant polyphenols and also identify oil palm fronds as containing constituents that promote vascular relaxation via endothelium-dependent mechanisms.
Phosphatidylethanolamine N-methyltransferase (PEMT) governs the secretion of hepatic triglycerides in the form of very low-density lipoprotein and has been implicated in nonalcoholic fatty liver disease (NAFLD). Studies on the role of the PEMT rs7946 polymorphism as a genetic modifier of NAFLD have reported inconsistent results. This meta-analysis was carried out to evaluate and summarize the association of PEMT rs7946 with susceptibility to NAFLD.
Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase. The loss of these catabolic enzymes was accompanied by the loss of cellular ATP and lower lactate generation. Addition of the macrophage antioxidant 7,8-dihydroneopterin inhibited the ROS generation, glutathione loss and catabolic inactivation. NOX was shown to be activated by oxLDL addition while apocynin inhibited the loss of GSH and cell viability. The data suggests that oxLDL triggers an excess of ROS production through NOX activation, and catabolic failure through thiol oxidation resulting in cell death.
The oxidative susceptibilities of low density lipoproteins (LDL) isolated from rabbits fed high-fat atherogenic diets containing coconut, palm, or soybean oil were investigated. New Zealand white rabbits were fed atherogenic semisynthetic diets containing 0.5% cholesterol and either (i) 13% coconut oil and 2% corn oil (CNO), (ii) 15% refined, bleached, and deodorized palm olein (RBDPO), (iii) 15% crude palm olein (CPO), (iv) 15% soybean oil (SO), or (v) 15% refined, bleached, and deodorized palm olein without cholesterol supplementation [RBDPO(wc)], for a period of twelve weeks. Total fatty acid compositions of the plasma and LDL were found to be modulated (but not too drastically) by the nature of the dietary fats. Cholesterol supplementation significantly increased the plasma level of vitamin E and effectively altered the plasma composition of long-chain fatty acids in favor of increasing oleic acid. Oxidative susceptibilities of LDL samples were determined by Cu2(+)-catalyzed oxidation which provide the lag times and lag-phase slopes. The plasma LDL from all palm oil diets [RBDPO, CPO, and RBDPO(wc)] were shown to be equally resistant to the oxidation, and the LDL from SO-fed rabbits were most susceptible, followed by the LDL from the CNO-fed rabbits. These results reflect a relationship between the oxidative susceptibility of LDL due to a combination of the levels of polyunsaturated fatty acids and vitamin E.
Antioxidants are substances that may protect cells from the damage caused by unstable molecules such as free radicals. Flavonoids are phenolic substances widely found in fruits and vegetables. The previous studies showed that the ingestion of flavonoids reduces the risk of cardiovascular diseases, metabolic disorders, and certain types of cancer. These effects are due to the physiological activity of flavonoids in the reduction of oxidative stress, inhibiting low-density lipoproteins oxidation and platelet aggregation, and acting as vasodilators in blood vessels. Free radicals are constantly generated resulting in extensive damage to tissues leading to various disease conditions such as cancer, Alzheimer's, renal diseases, cardiac abnormalities, etc., Medicinal plants with antioxidant properties play a vital functions in exhibiting beneficial effects and employed as an alternative source of medicine to mitigate the disease associated with oxidative stress. Flavonoids have existed over one billion years and possess wide spectrum of biological activities that might be able to influence processes which are dysregulated in a disease. Quercetin, a plant pigment is a potent antioxidant flavonoid and more specifically a flavonol, found mostly in onions, grapes, berries, cherries, broccoli, and citrus fruits. It is a versatile antioxidant known to possess protective abilities against tissue injury induced by various drug toxicities.