Mushrooms have been highly regarded as possessing enormous nutritive and medicinal values. In the present study, we evaluated the anti-oxidative and anti-atherosclerotic potential of shiitake mushroom () using its solvent-solvent partitioned fractions that consisted of methanol:dichloromethane (M:DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA) and aqueous residue (AQ). The hexane fraction (1 mg/mL) mostly scavenged (67.38%, IC0.55 mg/mL) the 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radical, contained the highest reducing capacity (60.16 mg gallic acid equivalents/g fraction), and most potently inhibited lipid peroxidation (67.07%), low density lipo-protein oxidation and the activity of 3-hydroxy 3-methyl glutaryl co-enzyme A reductase (HMGR). GC-MS analyses of the hexane fraction identified-tocopherol (vitamin E), oleic acid, linoleic acid, ergosterol and butyric acid as the bio-functional components present inOur findings suggest thatpossesses anti-atherosclerotic bio-functionality that can be applied as functional food-based therapeutics against cardiovascular diseases.

Certain drastic behavioral modifications by arterial wall smooth muscle cells (SMC) have been considered key steps in the formation of atherosclerotic lesions: massive migration of SMC from the media to the intima layer of the vessel, dedifferentiation of SMC to proliferating phenotype, and increased secretion of inflammatory cytokines as a response to inflammatory stimuli. We investigated the anti-atherogenic effects of naturally occurring compounds (ascorbic acid, green tea extract, lysine, proline, arginine, and N-acetyl cysteine) using the model of cultured aortic SMC. Cell growth was measured by DNA synthesis, cell invasiveness was measured through Matrigel, matrix metalloproteinase-2 (MMP-2) secretion was measured by zymography, and SMC secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) was measured by immunochemistry. Fetal bovine serum-stimulated SMC growth was inhibited by the nutrient mixture (NM) with 85% inhibition at 100 microg/mL. A corresponding concentration of epigallocatechin gallate (EGCG; 15 microM), the most active tea phenolic, produced a significant effect but one lower than NM. NM inhibited aortic SMC Matrigel invasion in a dose-dependent manner and significantly decreased MMP-2 expression. Stimulation of SMC with tumor necrosis factor-alpha significantly increased production and secretion of such mediators of inflammation as IL-6 and MCP-1; addition of 100 microg/mL NM inhibited secretion of MCP-1 and IL-6 by 65% and 47%, respectively. These data suggest that the NM of ascorbic acid, tea phenolics, and selected amino acids has potential in blocking the development of atherosclerotic lesions by inhibiting atherogenic responses of vascular SMC to pathologic stimuli and warrants in vivo studies.

Atherosclerosis is a progressive and multifactorial disease which occurs under the influence of various risk factors including endothelial dysfunction (ED), oxidative stress, and low-density lipoprotein (LDL) oxidation. In contract to the initial hypotheses on the usefulness of vitamin E supplementation for cardiovascular disease prevention, large outcome trials showed consumption of vitamin E has no obvious effect on cardiovascular disease and, in some cases, it may even increase the rate of mortality. This seemingly unexpected finding may be due to the opposite effects of vitamin E compounds. Vitamin E is a group of compounds which have different and even opposing effects, yet in most of the studies, the exact consumed component of vitamin E is not determined. It appears that the combined consumption of gamma-tocopherol, vitamin C, vitamin D, and tetrahydrobiopterin (BH4) may be extremely effective in both preventing atherogenesis and suppressing plaque development. In this regard, one of main issues is effect of vitamin E and D deficiency on microRNAs network in atherosclerosis. Various studies have indicated that miRNAs have key roles in atherosclerosis pathogenesis. The deficiency of vitamin E and D could provide a deregulation for miRNAs network and these events could lead to progression of atherosclerosis. Here, we highlighted a variety of mechanisms involve in the progression of atherosclerosis and effects of vitamin D and E on these mechanisms. Moreover, we summarized miRNAs involve in atherosclerosis and their regulation by vitamin E and D deficiency. This article is protected by copyright. All rights reserved.

BACKGROUND:In the setting of atherosclerosis, endothelial vasomotor function is abnormal. Increased oxidative stress has been implicated as one potential mechanism for this observation. We therefore hypothesized that an antioxidant, ascorbic acid, would improve endothelium-dependent arterial dilation in patients with coronary artery disease.

METHODS AND RESULTS:Brachial artery endothelium-dependent dilation in response to hyperemia was assessed by high-resolution vascular ultrasound before and 2 hours after oral administration of either 2 g ascorbic acid or placebo in a total of 46 patients with documented coronary artery disease. Plasma ascorbic acid concentration increased 2.5-fold 2 hours after treatment (46+/-8 to 114+/-11 micromol/L, P=.001). In the prospectively defined group of patients with an abnormal baseline response (<5% dilation), ascorbic acid produced marked improvement in dilation (2.0+/-0.6% to 9.7+/-2.0%), whereas placebo had no effect (1.1+/-1.5% to 1.7+/-1.5%, P=.003 for ascorbic acid versus placebo). Ascorbic acid had no effect on hyperemic flow or arterial dilation to sublingual nitroglycerin.

CONCLUSIONS:Ascorbic acid reverses endothelial vasomotor dysfunction in the brachial circulation of patients with coronary artery disease. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in patients with atherosclerosis and that endothelial dysfunction may respond to antioxidant therapy.

Platelet activation, including the formation of monocyte platelet aggregates (MPAs), contributes to atherosclerosis, thrombus formation and acute coronary syndromes. Regular participation in exercise can lower cardiovascular risk, but little is known regarding the impact of exercise training on platelet function. We investigated the effect of 6 months of walking exercise on platelet function in sedentary older adults without significant cardiovascular disease. Twenty-seven participants were randomly allocated to 6 months of either: no-exercise (n=13) or 3 x 50 mins/wk of supervised centre-based walking (n=14). Circulating and agonist induced MPAs were assessed using flow cytometry before (month 0 0M) and after (month 6 6M) the intervention. Circulating MPAs increased from 0M (3.7 {plus minus} 1.0%) to 6M (4.7 {plus minus} 1.6%) in the no-exercise group (P = 0.009), whereas a non-significant decrease was observed in the walking group (0M 4.3 {plus minus} 1.7% vs 6M 3.7 {plus minus} 1.2, P = 0.052). The change in MPAs between groups was significant (P = 0.001). There were no differences between groups in platelet responses to agonists across the interventions (all P>0.05). Collectively, these data suggest that the absence of regular exercise may increase MPAs, which are cellular mediators involved in atherosclerosis, whilst regular walking inhibits such increases. The thrombotic function of platelets appear to be relatively unaltered by exercise training. This study provides novel data related to the cardio-protective effects associated with participation in exercise.

Understanding the interactions between sleep and the immune system may offer insight into why short sleep duration has been linked to negative health outcomes. We, therefore, investigated the effects of napping and extended recovery sleep after sleep restriction on the immune and inflammatory systems and sleepiness. After a baseline night, healthy young men slept for a 2-h night followed by either a standard 8-h recovery night (n=12), a 30-min nap (at 1 p.m.) in addition to an 8-h recovery night (n=10), or a 10-h extended recovery night (n=9). A control group slept 3 consecutive 8-h nights (n=9). Subjects underwent continuous electroencephalogram polysomnography and blood was sampled every day at 7 a.m. Leukocytes, inflammatory and atherogenesis biomarkers (high-sensitivity C-reactive protein, interleukin-8, myeloperoxidase, fibrinogen and apolipoproteins ApoB/ApoA), sleep patterns and sleepiness were investigated. All parameters remained unchanged in the control group. After sleep restriction, leukocyte and - among leukocyte subsets - neutrophil counts were increased, an effect that persisted after the 8-h recovery sleep, but, in subjects who had a nap or a 10-h recovery sleep, these values returned nearly to baseline. Inflammatory and atherogenesis biomarkers were unchanged except for higher myeloperoxidase levels after sleep restriction. The increased sleepiness after sleep restriction was reversed better in the nap and extended sleep recovery conditions. Saliva cortisol decreased immediately after the nap. Our results indicate that additional recovery sleep after sleep restriction provided by a midday nap prior to recovery sleep or a sleep extended night can improve alertness and return leukocyte counts to baseline values.

A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes. In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-kappaB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs). HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-kappaB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs. Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment. Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis.

The biochemical mechanisms by which hypertension accelerates atherosclerosis and increases the risk of aortic aneurysm rupture are poorly understood. This study evaluates the effects of hypertension on aortic trace element concentrations and antioxidant status in tissue removed from 26 normotensive (NT) and 20 hypertensive (HT) patients. Twenty-seven of 46 patients (59%) had aneurysmal (AA), and 19 of 46 (41%) had occlusive disease (OD). Aortic iron concentrations were markedly higher in both OD and AA tissue compared with controls. A similar trend was observed with copper concentrations, with the highest elevations observed in HT AA tissues. No significant differences were observed in zinc concentrations, except that HT AA aorta had significantly lower zinc levels than either OD or control tissue. Aortic ascorbic acid concentrations in diseased aorta were lower than those of controls, but independent of blood pressure. Copper-zinc-superoxide dismutase activity was similarly reduced, with the lowest activity observed in diseased aorta from HT patients. Only HT AA aorta had significantly higher manganese-superoxide dismutase activity than controls. The aortas of patients with AA had significantly lower amounts of elastin and greater elastase activity than either controls or those with OD. However, the differences were independent of blood pressure. Hypertensive patients with OD and AA had 31% more and 27% less aortic collagen, respectively, than their NT counterparts (P less than 0.05). These data suggest that the reduction in aortic collagen and elastin in HT patients with AA compared with their NT counterparts may explain the larger size of aneurysms and predispose to their eventual rupture. Furthermore, the diminished antioxidant status associated with HT predisposes to lipid peroxidation, which contributes to the acceleration of these processes. Our studies were conducted in patients with established aortic aneurysmal and occlusive disease. Whether these observations are pertinent to the pathogenesis of AA and OD remains unclear and merits further study.

Consumption of a high-fat, high-sugar diet and sedentary lifestyle are correlated with bulk arterial stiffening. While measurements of bulk arterial stiffening are used to assess cardiovascular health clinically, they cannot account for changes to the tissue occurring on the cellular scale. The compliance of the subendothelial matrix in the intima mediates vascular permeability, an initiating step in atherosclerosis. High-fat, high-sugar diet consumption and a sedentary lifestyle both cause micro-scale subendothelial matrix stiffening, but the impact of these factors in concert remains unknown. In this study, mice on a high-fat, high-sugar diet were treated with aerobic exercise or returned to a normal diet. We measured bulk arterial stiffness through pulse wave velocity and subendothelial matrix stiffness ex vivo through atomic force microscopy. Our data indicate that while diet reversal mitigates high-fat, high-sugar diet-induced macro- and micro-scale stiffening, exercise only significantly decreases micro-scale stiffness and not macro-scale stiffness, during the time-scale studied. These data underscore the need for both healthy diet and exercise to maintain vascular health. These data also indicate that exercise may serve as a key lifestyle modification to partially reverse the deleterious impacts of high-fat, high-sugar diet consumption, even while macro-scale stiffness indicators do not change.

Coronary heart disease is the major cause of global cardiovascular mortality and morbidity. Lifestyle behaviour contributes as a risk factor: unhealthy diet, sedentary lifestyle, tobacco, alcohol, hypertension, diabetes, dyslipidemia and psychosocial stress. Atherosclerosis pathologic mechanisms involving oxidative stress, dyslipidemia, inflammation and senescence are associated with arterial wall damage and plaque formation. Stress reduction was observed in several types of meditation. After meditation, hormonal orchestration modulates effects in the central nervous system and in the body. All types of meditation are associated with blood pressure control, enhancement in insulin resistance, reduction of lipid peroxidation and cellular senescence, independent of type of meditation. This review presents scientific evidence to explain how meditation can produce beneficial effects on the cardiovascular system, and particularly regarding vascular aspects.

BACKGROUND:Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Activation or injury of the endothelium leads to a variety of inflammatory disorders, including the release of microparticles. Endothelial progenitor cells may contribute to the maintenance of the endothelium by replacing injured mature endothelial cells.

OBJECTIVE:We studied the influence of dietary fat on the release of endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) in elderly subjects.

DESIGN:Twenty healthy, elderly subjects (10 men and 10 women) consumed 3 diets following a randomized crossover design, each for 4 wk: a saturated fatty acid diet; a low-fat, high-carbohydrate diet; and a Mediterranean diet (MedDiet) enriched in monounsaturated fatty acids. We investigated total microparticles, EMPs from activated endothelial cells (activated EMPs), EMPs from apoptotic endothelial cells (apoptotic EMPs), EPCs, oxidative stress variables, and ischemic reactive hyperemia (IRH).

RESULTS:The MedDiet led to lower total microparticle, activated EMP, and apoptotic EMP concentrations and higher EPC numbers than did the other diets (P<0.001). We detected lower superoxide dismutase activity (P<0.001), a higher plasmaβ-carotene concentration (P<0.001), and lower urinary isoprostane and plasma nitrotyrosine concentrations after consumption of the MedDiet than after consumption of the other 2 diets (P<0.05). Furthermore, the occurrence of IRH was higher after consumption of the MedDiet than after consumption of the other 2 diets (P<0.05).

CONCLUSION:Consumption of the MedDiet induces a reduction in endothelial damage and dysfunction, which is associated with an improvement in the regenerative capacity of the endothelium, in comparison with 2 other diets.

Several studies indicated how dietary patterns that were obtained from nutritional cluster analysis can predict disease risk or mortality. Low-grade chronic inflammation represents a background pathogenetic mechanism linking metabolic risk factors to increased risk of chronic degenerative diseases. A Mediterranean diet (MeDi) style has been reported as associated with a lower degree of inflammation biomarkers and with a protective role on cardiovascular and cerebrovascular events. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. Recently, it has been reported a novel positive association between baseline plasma ceramide concentrations and cardiovascular events and how adherence to a Mediterranean Diet-style may influence the potential negative relationship between elevated plasma ceramide concentrations and cardiovascular diseases (CVD). Several randomized controlled trials (RCTs) showed the positive effects of the MeDi diet style on several cardiovascular risk factors, such as body mass index, waist circumference, blood lipids, blood pressure, inflammatory markers and adhesion molecules, and diabetes and how these advantages of the MeDi are maintained in comparison of a low-fat diet. Some studies reported a positive effect of adherence to a Mediterranean Diet and heart failure incidence, whereas some recent studies, such as the PREDIMED study, showed that the incidence of major cardiovascular events was lower among those assigned to MeDi supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. New studies are needed to better understand the molecular mechanisms, whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases, but also discussing other related diseases. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a review of the clinical effects of this dietary style underlying the biochemical and molecular effects of the Mediterranean diet. Our purpose is to review the main features of the Mediterranean diet in particular its benefits on human health, underling the anti-inflammatory, anti-oxidant and anti-atherosclerotic effects to which new knowledge about epigenetic and gut-microbiota relationship is recently added.

The dried, immature fruit of Citrus aurantium L., 'Zhiqiao' in Chinese, has been used to treat cardiovascular diseases in traditional Chinese medicine for centuries. Naringenin and hesperetin and their glycosides present in considerable amounts (about 10 approximately 15%) in the herb. The aim of this study is to test whether naringenin and hesperetin influence adiponectin expression, which plays an important role in glucose and lipid metabolism with antiatherogenic and anti-inflammatory properties. Treatment with naringenin and hesperetin enhanced adiponectin transcription in differentiated 3T3-L1 cells. Both naringenin and hesperetin induced peroxisome proliferator-activated receptor (PPAR)gamma-controlled luciferase expression in a dose-dependent manner (20-160 microM), whereas only naringenin possessed significant activity to activate PPARalpha. These results suggested the two flavonoids might exert antiatherogenic effects partly through activating PPAR and up-regulating adiponectin expression in adipocytes. Our findings give new insight for the molecular explanations for the therapeutic effects of Zhiqiao. Copyright (c) 2008 John Wiley & Sons, Ltd.

BACKGROUND:Physical activity is associated with reduced cardiovascular disease risk, mainly through effects on atherosclerosis. Aortic stiffness may be an alternative mechanism. We examined whether patterns of physical activity and sedentary behavior are associated with rate of aortic stiffening.

METHODS AND RESULTS:Carotid-femoral pulse wave velocity (PWV) was measured twice using applanation tonometry at mean ages 65 (in 2008/2009) and 70 (in 2012/2013) years in the Whitehall-II study (N=5196). Physical activity was self-reported at PWV baseline (2008/2009) and twice before (in 1997/1999 and 2002/2003). Sedentary time was defined as sitting time watching television or at work/commute. Linear mixed models adjusted for metabolic and lifestyle risk factors were used to analyze PWV change. Mean (SD) PWV (m/s) was 8.4 (2.4) at baseline and 9.2 (2.7) at follow-up, representing a 5-year increase of 0.76 m/s (95% CI 0.69, 0.83). A smaller 5-year increase in PWV was observed for each additional hour/week spent in sports activity (-0.02 m/s [95% CI -0.03, -0.001]) or cycling (-0.02 m/s [-0.03, -0.008]). Walking, housework, gardening, or do-it-yourself activities were not significantly associated with aortic stiffening. Each additional hour/week spent sitting was associated with faster PWV progression in models adjusted for physical activity (0.007 m/s [95% CI 0.001, 0.013]). Increasing physical activity over time was associated with a smaller subsequent increase in PWV (-0.16 m/s [-0.32, -0.002]) compared with not changing activity levels.

CONCLUSIONS:Higher levels of moderate-to-vigorous physical activity and avoidance of sedentary behavior were each associated with a slower age-related progression of aortic stiffness independent of conventional vascular risk factors.

Oxidative stress, inflammation, and foam cell formation in vascular smooth muscle cells (VSMCs) are considered to play crucial roles in the pathogenesis of atherosclerosis. Poria cocos polysaccharides (PCP) has been shown to possess anti-inflammatory, antitumor and anti-oxidative properties. In this study we explored the effects of PCP on ox-LDL-induced inflammation, oxidative stress and foam cell formation in VSMCs. PCP significantly attenuated ox-LDL-induced oxidative stress, as evidenced by the decreased reactive oxygen species (ROS) and MDA levels, and the increased SOD activity in VSMCs. PCP suppressed the induction effect of ox-LDL on inflammatory cytokines and inflammatory mediators. PCP also substantially inhibited VSMCs foam cell formation and intracellular lipids accumulation. Mechanistically, PCP suppressed ox-LDL-induced up-regulation of LOX-1, which is responsible for ox-LDL uptake. Western blotting suggested that PCP activated ERK1/2 signaling pathway, increased Nrf2 translocated from cytoplasm to nucleus and heme oxygenase-1 (HO-1) expression. Up-regulation of PCP on Nrf2/HO-1 signaling was reversed by pretreatment with ERK inhibitor PD98059, indicating the involvement of ERK in PCP activation of Nrf2/HO-1 signaling. In conclusion, these results demonstrated that PCP exerted its protection against oxidative stress and inflammation via the ERK/Nrf2/HO-1 signaling pathway and that PCP may be a promising candidate for the therapy of atherosclerosis.

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 withdrawnvia 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.

Bengal gram seed coat appeared to be a potent hypocholesterolemic/hypolipidemic agent in rabbits. When fed to hypercholesterolemic rabbits, it lowered hepatic cholesterol/lipid much more than in the control group. Aortic lipid levels were rather marginally increased but the increase was less in Bengal gram seed coat fed rabbits. Though seed coat of Bengal gram failed to prevent the development of atherosclerosis in hypercholesterolemic rabbits, but certainly it slowed down the process of its development. The hypocholesterolemic action of Bengal gram seed coat appeared to be due to the increased catabolism and excretion of cholesterol.

Chronic low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease and type 2 diabetes. Regular exercise offers protection against all-cause mortality, primarily by protection against atherosclerosis and insulin resistance and there is evidence that physical training is effective as a treatment in patients with chronic heart diseases and type 2 diabetes. Regular exercise induces anti-inflammatory actions. During exercise, IL-6 (interleukin-6) is produced by muscle fibres. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra (interleukin-1 receptor antagonist) and IL-10 (interleukin-10) and inhibits the production of the pro-inflammatory cytokine TNF-alpha (tumour necrosis factor-alpha). In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. It is suggested that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine, that is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body. Myokines may be involved in mediating the beneficial health effects against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.

Folk medicine stories accredited the aptitude of camel milk (CMK) as a hypoglycemic agent and recent studies have confirmed this in the diabetic patients and experimental animals. However, the mechanism(s) by which CMK influences glucose homeostasis is yet unclear. The current study investigated the changes in the glucose homeostatic parameters, the incretin hormones, and the inflammatory cytokines in the CMK-treated diabetic animals. A model of type 2 diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin 40 mg/kg/day for 4 repeated doses. Camel milk treatment was administered for 8 weeks. The changes in glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic peptide (GIP), glucose tolerance, fasting and glucose-stimulated insulin secretion, insulin resistance (IR), TNF-α, TGF-β1, lipid profile, atherogenic index (AI), and body weight were investigated. The untreated diabetic animals showed hyperglycemia, increased HOMA-IR, hyperlipidemia, elevated AI, high serum incretins [GLP-1 and GIP], TNF-α, and TGF-β1 levels and weight loss as compared with the control group. Camel milk treatment to the diabetic animals resulted in significant lowered fasting glucose level, hypolipidemia, decreased HOMA-IR, recovery of insulin secretion, weight gain, and no mortality during the study. Additionally, CMK inhibits the diabetes-induced elevation in incretin hormones, TNF-α and TGF-β1 levels. The increase in glucose-stimulated insulin secretion, decreased HOMA-IR, modulation of the secretion and/or the action of incretins, and the anti-inflammatory effect are anticipated mechanisms to the antidiabetic effect of CMK and suggest it as a valuable adjuvant antidiabetic therapy.

Humans are not programmed to be inactive. The combination of both accelerated sedentary lifestyle and constant food availability disturbs ancient metabolic processes leading to excessive storage of energy in tissue, dyslipidaemia and insulin resistance. As a consequence, the prevalence of Type 2 diabetes, obesity and the metabolic syndrome has increased significantly over the last 30 years. A low level of physical activity and decreased daily energy expenditure contribute to the increased risk of cardiovascular morbidity and mortality following atherosclerotic vascular damage. Physical inactivity leads to the accumulation of visceral fat and consequently the activation of the oxidative stress/inflammation cascade, which promotes the development of atherosclerosis. Considering physical activity as a 'natural' programmed state, it is assumed that it possesses atheroprotective properties. Exercise prevents plaque development and induces the regression of coronary stenosis. Furthermore, experimental studies have revealed that exercise prevents the conversion of plaques into a vulnerable phenotype, thus preventing the appearance of fatal lesions. Exercise promotes atheroprotection possibly by reducing or preventing oxidative stress and inflammation through at least two distinct pathways. Exercise, through laminar shear stress activation, down-regulates endothelial AT1R (angiotensin II type 1 receptor) expression, leading to decreases in NADPH oxidase activity and superoxide anion production, which in turn decreases ROS (reactive oxygen species) generation, and preserves endothelial NO bioavailability and its protective anti-atherogenic effects. Contracting skeletal muscle now emerges as a new organ that releases anti-inflammatory cytokines, such as IL-6 (interleukin-6). IL-6 inhibits TNF-α (tumour necrosis factor-α) production in adipose tissue and macrophages. The down-regulation of TNF-α induced by skeletal-muscle-derived IL-6 may also participate in mediating the atheroprotective effect of physical activity.