Vitamin D and Calcium Supplementation Accelerate Vascular Calcification in a Model of Pseudoxanthoma Elasticum.

Arterial calcification is a common feature of pseudoxanthoma elasticum (PXE), a disease characterized by ABCC6 mutations, inducing a deficiency in pyrophosphate, a key inhibitor of calcium phosphate crystallization in arteries. METHODS: we analyzed whether long-term exposure of Abcc6-/- mice (a murine model of PXE) to a mild vitamin D supplementation, with or without calcium, would impact the development of vascular calcification. Eight groups of mice (including Abcc6-/- and wild-type) received vitamin D supplementation every 2 weeks, a calcium-enriched diet alone (calcium in drinking water), both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Aorta and kidney artery calcification was assessed by 3D-micro-computed tomography, Optical PhotoThermal IR (OPTIR) spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) and Yasue staining. RESULTS: at 6 months, although vitamin D and/or calcium did not significantly increase serum calcium levels, vitamin D and calcium supplementation significantly worsened aorta and renal artery calcification in Abcc6-/- mice. CONCLUSIONS: vitamin D and/or calcium supplementation accelerate vascular calcification in a murine model of PXE. These results sound a warning regarding the use of these supplementations in PXE patients and, to a larger extent, patients with low systemic pyrophosphate levels.

Losartan protects endothelium-dependent relaxation in vivo in a murine model of rheumatoid arthritis.

Angiotensin II-type 1 receptor stimulation is recognised to promote inflammation, a state central to the development and maintenance of rheumatoid arthritis. Herein we examined the use of losartan, an angiotensin II-type 1 receptor antagonist, on vascular reactivity, knee joint diameter and behavioural assessment of pain in a Freund's complete adjuvant (FCA) mouse model of joint inflammation. Monoarthritis was induced via FCA in the presence or absence of losartan with naive mice serving as controls. Knee joint swelling, joint pain (assessed by dynamic weight bearing of limb use), knee joint artery reactivity (assessed ex vivo) and blood perfusion of the knee joint (assessed in vivo) were determined. FCA mediated a significant increase in knee joint diameter and reduced weight-bearing (a surrogate for pain sensation) of the affected limb. Notably, these phenomena were substantially reduced when mice were prophylactically treated with losartan. Assessment of arterial relaxation and blood perfusion with acetylcholine stimulation revealed that FCA resulted in significant vascular dysfunction, which was resolved to naïve levels with losartan treatment. Through the actions of losartan, these findings indicate that the angiotensin II-type 1 receptor is a likely therapeutic target of importance in the development of the physical changes, pain sensation and vascular dysfunction found in inflammatory arthritis.

Differential Deleterious Impact of Highly Saturated Versus Monounsaturated Fat Intake on Vascular Function, Structure, and Mechanics in Mice.

Vegetable oils such as palm oil (enriched in saturated fatty acids, SFA) and high-oleic-acid sunflower oil (HOSO, containing mainly monounsaturated fatty acids, MUFA) have emerged as the most common replacements for trans-fats in the food industry. The aim of this study is to analyze the impact of SFA and MUFA-enriched high-fat (HF) diets on endothelial function, vascular remodeling, and arterial stiffness compared to commercial HF diets. Five-week-old male C57BL6J mice were fed a standard (SD), a HF diet enriched with SFA (saturated oil-enriched Food, SOLF), a HF diet enriched with MUFA (unsaturated oil-enriched Food, UOLF), or a commercial HF diet for 8 weeks. Vascular function was analyzed in the thoracic aorta. Structural and mechanical parameters were assessed in mesenteric arteries by pressure myography. SOLF, UOLF, and HF diet reduced contractile responses to phenylephrine and induced endothelial dysfunction in the thoracic aorta. A significant increase in the ß-index, and thus in arterial stiffness, was also detected in mesenteric arteries from the three HF groups, due to enhanced deposition of collagen in the vascular wall. SOLF also induced hypotrophic inward remodeling. In conclusion, these data demonstrate a deleterious effect of HF feeding on obesity-related vascular alterations that is exacerbated by SFA.

Therapeutic effect of Jianpi Liqi Fang combined with transcatheter arterial chemoembolization in patients with hepatocellular carcinoma and spleen deficiency syndrome.

OBJECTIVE: To investigate the therapeutic effect of the Jianpi Liqi Fang ( ，JPLQF) combined with transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and spleen deficiency syndrome (SDS) and identify a potential indicator of efficacy. METHODS: Ninety-nine patients with HCC who were diagnosed with SDS, non-spleen deficiency syndrome (NSDS), or no syndrome (NS) were treated with JPLQF combined with TACE for three periods. Therapeutic efficacy was compared among the groups. Plasma proteins were screened using label-free discovery analysis and verified via enzyme-linked immunosorbent assay (ELISA). Furthermore, receiver operating characteristic (ROC) curves were analyzed to evaluate therapeutic indicators. RESULTS: After treatment, the Karnofsky Performance Status was significantly improved in the SDS group and significantly better than that in the NS group. The Traditional Chinese Medicine (TCM) syndrome scores were lower in the SDS group after treatment and lower than those in the NSDS group. However, alanine aminotransferase, carbohydrate antigen 19-9, alpha-fetoprotein, and carcinoembryonic antigen levels and white blood cell and platelet counts did not differ among the groups. Serum aspartate aminotransferase levels in the SDS group were significantly lower after treatment than before treatment, and total bilirubin levels were significantly lower in the SDS group than in the NSDS group. Label-free analysis identified 24 differentially expressed proteins (DEPs) between the SDS and NS groups, including 17 and 7 upregulated and downregulated proteins, respectively. Fibulin-5 (FBLN5) displayed the largest difference in expression between the groups. ELISA confirmed that FBLN5 levels were significantly lower in the NSDS and NS groups than in the SDS group. Following treatment with JPLQF and TACE, FBLN5 expression was upregulated only in the SDS group. Furthermore, ROC curve analysis indicated that FBLN5 may serve as a potential indicator of the efficacy of JPLQF combined with TACE in patients with HCC and SDS. CONCLUSION: JPLQF combined with TACE improved quality of life, clinical TCM symptoms, and liver function in patients with HCC and SDS. FBLN5 expression was significantly altered by treatment with JPLQF and TACE in patients with HCC and SDS.

Moringa oleifera leaf extract enhances endothelial nitric oxide production leading to relaxation of resistance artery and lowering of arterial blood pressure.

A mass of evidence has identified a promoting of nitric oxide (NO) production in endothelial cells using natural products as a potential strategy to prevent and treat hypertension. This study investigated whether the aqueous extract of Moringa oleifera leaves (MOE) could lower mean arterial pressure (MAP) and relax mesenteric arterial beds in rats via stimulating endothelium-derived NO production. Intravenous administration of MOE (1-30 mg/kg) caused a dose-dependent reduction in MAP in anesthetized rats. In rats pretreated with the NO-synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg, i.v.), the effect of MOE on MAP was significantly reduced. MOE (0.001-3 mg) induced relaxation in methoxamine (10 µM) pre-contracted mesenteric arterial beds, which was abolished by endothelium denudation. This endothelium-dependent vasorelaxation was reduced by L-NAME (100 µM) or the NO-sensitive guanylyl cyclase inhibitor, 1H- [1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (10 µM). In primary human pulmonary artery endothelial cells, MOE (3-30 µg/mL) induced NO production, which was inhibited by L-NAME (100 µM) pretreatment. These findings show that MOE stimulates the endothelium-derived NO release for driving its vasorelaxation to lower arterial blood pressure. These suggest the development of MOE as a natural antihypertensive supplement.

Polydatin for treating atherosclerotic diseases: A functional and mechanistic overview.

With the advancement of science and technology, the living standards of human beings have continuously improved, but the incidence and mortality from atherosclerosis worldwide have also increased by year. Although interventional surgery and the continuous development of new drugs have significant therapeutic effects, their side effects cannot be ignored. Polydatin, an active ingredient isolated from the natural medicine Polygonum cuspidatum, has been shown to have a prominent role in the treatment of cardiovascular diseases. Polydatin treats atherosclerosis mainly from three aspects: anti-inflammatory, regulating lipid metabolism and anti-oxidative stress. This article will review the pharmacological mechanism of polydatin in anti-atherosclerosis, the biological characteristics of Polygonum cuspidatum, the toxicology and pharmacokinetics of polydatin and will provide ideas for further research.

New Insight into the Mechanisms of Ginkgo Biloba Extract in Vascular Aging Prevention.

BACKGROUND: Aging-associated vascular dysfunction promotes cardiovascular diseases. Recently, Ginkgo biloba extract (GBE) has attracted considerable attention in the prevention of aged vasculature. METHODS: This review discusses the pathophysiological alterations in aged vasculature and the underlying mechanisms of GBE in vascular aging suppression. RESULTS: Both arterial stiffening and endothelial dysfunction are critical aging-related vascular phenotypes that result in the progression of cardiovascular diseases in the general population. Consistent oxidative stress and inflammatory reaction lead to vascular dysfunction. GBE ameliorates aging-related vascular dysfunction, due to its antioxidant and anti-inflammatory properties. The main effects of GBE in aged vasculature might be associated with the longevity signaling pathways. GBE also attenuates the progression of vascular aging in diabetes mellitus via regulation of glucose and lipid metabolism. CONCLUSION: GBE plays an important role in the prevention of vascular aging process. It is a promising therapeutic approach to ameliorate aging-related vascular dysfunction and cardiovascular diseases.

[Comparison of efficacy of rivaroxaban and warfarin after open operations on the infrainguinal segment]. / Sravnenie éffektivnosti rivaroksabana i varfarina posle otkrytykh operatsii na infraingvinal'nom segmente.

The authors analysed oral anticoagulant agents prescribed in the postoperative period to patients after endured reconstructive operative intervention on arteries of the femorotibial segment. The study included a total of 104 patients subjected to femoropopliteal or femorotibial bypass grafting using an autologous vein or a prosthesis. Depending on the prescribed anticoagulation agent, the patients were subdivided into two groups. Group One patients (n=43) in the postoperative period received rivaroxaban, and Group Two patients (n=61) took warfarin. Efficacy of therapy was evaluated by the frequency of haemorrhage and thromboses in the early and remote postoperative periods. The findings of the immediate postoperative period demonstrated comparable rates of haemorrhagic complications, early thromboses and redo interventions in both Groups (p=0.7). The duration of long-term postoperative period varied from 3 months to 5 years. No statistically significant differences in patency of the performed reconstructions were revealed between the groups. The 3-year primary assisted patency rate in the rivaroxaban group and warfarin group amounted to 89 and 80%, respectively. The incidence of haemorrhagic complications in the postoperative period was insignificant in the studied groups. Hence, rivaroxaban may be prescribed in the early and remote postoperative period to patients who underwent open reconstructive operative intervention on arteries of the infrainguinal zone.

Vitamin D as A Protector of Arterial Health: Potential Role in Peripheral Arterial Disease Formation.

Atherosclerotic occlusive diseases and aneurysms that affect large and medium-sized arteries outside the cardiac and cerebral circulation are collectively known as peripheral arterial disease (PAD). With a rise in the rate of aging population worldwide, the number of people diagnosed with PAD is rapidly increasing. The micronutrient vitamin D is an important steroid hormone that acts on many crucial cellular mechanisms. Experimental studies suggest that optimal levels of vitamin D have beneficial effects on the heart and blood vessels; however, high vitamin D concentrations have been implicated in promoting vascular calcification and arterial stiffness. Observations from various clinical studies shows that deficiency of vitamin D has been associated with a greater risk of PAD. Epidemiological studies have often reported an inverse relation between circulating vitamin D status measured in terms of 25-hydroxivitamin D [25(OH)D] levels and increased cardiovascular disease risk; however, randomized controlled trials did not show a consistent positive effect of vitamin D supplementation on cardiovascular disease risk or events. Even though PAD shares all the major risk factors with cardiovascular diseases, the effect of vitamin D deficiency in PAD is not clear. Current evidence suggests a strong role of vitamin D in promoting genomic and epigenomic changes. This review summarises the current literature that supports the notion that vitamin D deficiency may promote PAD formation. A better understanding of underlying pathological mechanisms will open up new therapeutic possibilities which is the main unmet need in PAD management. Furthermore, epigenetic evidence shows that a more holistic approach towards PAD prevention that incorporates a healthy lifestyle, adequate exercise and optimal nutrition may be more effective in protecting the genome and maintaining a healthy vasculature.

Regulation of calcific vascular and valvular disease by nuclear receptors.

PURPOSE OF REVIEW: This review addresses recent developments in studies of lipid regulation of calcific disease of arteries and cardiac valves, including the role of nuclear receptors. The role of lipid-soluble signals and their receptors is timely given the recent evidence and concerns that lipid-lowering treatment may increase the rate of progression of coronary artery calcification, which has been long associated with increased cardiovascular risk. Understanding the mechanisms will be important for interpreting such clinical information. RECENT FINDINGS: New findings support regulation of calcific vascular and valvular disease by nuclear receptors, including the vitamin D receptor, glucocorticoid receptor, nutrient-sensing nuclear receptors (liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors), and sex hormone (estrogen and androgen) receptors. There were two major unexpected findings: first, vitamin D supplementation, which was previously believed to prevent or reduce vascular calcification, showed no cardiovascular benefit in large randomized, controlled trials. Second, both epidemiological studies and coronary intravascular ultrasound studies suggest that treatment with HMG-CoA reductase inhibitors increases progression of coronary artery calcification, raising a question of whether there are mechanically stable and unstable forms of coronary calcification. SUMMARY: For clinical practice and research, these new findings offer new fundamental mechanisms for vascular calcification and provide new cautionary insights for therapeutic avenues.

Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect.

In randomised controlled trials (RCTs) of oral drug treatment of migraine attacks, efficacy is evaluated after 2 hours. The effect of oral naratriptan 2.5 mg with a maximum blood concentration (Tmax ) at 2 hours increases from 2 to 4 hours in RCTs. To check whether such a delayed effect is also present for other oral antimigraine drugs, we hand-searched the literature for publications on RCTs reporting efficacy. Two triptans, 3 nonsteroidal anti-inflammatory drugs (NSAIDs), a triptan combined with an NSAID and a calcitonin gene-related peptide receptor antagonist were evaluated for their therapeutic gain with determination of time to maximum effect (Emax ). Emax was compared with known Tmax from pharmacokinetic studies to estimate the delay to pain-free. The delay in therapeutic gain varied from 1-2 hours for zolmitriptan 5 mg to 7 hours for naproxen 500 mg. An increase in effect from 2 to 4 hours was observed after eletriptan 40 mg, frovatriptan 2.5 mg and lasmiditan 200 mg, and after rizatriptan 10 mg (Tmax  = 1 h) from 1 to 2 hours. This strongly indicates a general delay of effect in oral antimigraine drugs. A review of 5 possible effects of triptans on the trigemino-vascular system did not yield a simple explanation for the delay. In addition, Emax for triptans probably depends partly on the rise in plasma levels and not only on its maximum. The most likely explanation for the delay in effect is that a complex antimigraine system with more than 1 site of action is involved.

Overview of results from the Vitamin D Assessment (ViDA) study.

BACKGROUND: The Vitamin D Assessment (ViDA) study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy of monthly vitamin D supplementation in reducing the incidence of a range of acute and chronic diseases and intermediate outcomes. METHODS: The study was carried out in Auckland, New Zealand, among 5110 adults, aged 50-84 years, who were followed for a median 3.3 years. The intervention was vitamin D3 (2.5 mg or 100,000 IU) or placebo softgel oral capsules, mailed monthly to participants' homes, with two capsules sent in the first mail-out post-randomisation (i.e. 200,000 IU bolus, or placebo), followed 1 month later (and thereafter monthly) with 100,000 IU vitamin D3 or placebo capsules. Outcomes were monitored through routinely collected health data and self-completed questionnaires. RESULTS: The results showed no beneficial effect of vitamin D supplementation on incidence of cardiovascular disease, falls, non-vertebral fractures and all cancer. However, beneficial effects from vitamin D supplementation were seen: for persistence with taking statins in participants on long-term statin therapy; and also in bone mineral density and arterial function in participants with low 25-hydroxyvitamin D levels, and in lung function among ever smokers (especially if vitamin D deficient). The latter findings are consistent with several previous studies, CONCLUSION: Monthly high-dose vitamin D supplementation does not prevent a range of diseases, but may be beneficial for some intermediate outcomes in people who are vitamin D deficient. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry identifier: ACTRN12611000402943.

Influence of enhanced bioavailable curcumin on obesity-associated cardiovascular disease risk factors and arterial function: A double-blinded, randomized, controlled trial.

OBJECTIVES: This study aimed to determine whether an enhanced bioavailable curcumin formulation, CurQfen®, would improve circulating cardiovascular disease-related blood biomarkers and arterial function in young (age 18-35 y), obese (body mass index ≥ 30.0 kg/m2) men. METHODS: This double-blinded, placebo-controlled trial evaluated 22 men. The participants were matched based on body mass index and randomized to the intervention (curcumin formulated with fenugreek soluble fiber, for enhanced absorption) or control (fenugreek soluble fiber) group for 12 wk at 500mg/d without dietary modification or exercise. Blood samples and endothelial function measures were acquired at 0 and 12 wk, and blood samples were analyzed for cardiovascular disease-related blood biomarkers. Furthermore, central (aortic) blood pressure and augmentation index were monitored at 0, 4, 8, and 12 wk. RESULTS: After 12 wk of intervention, homocysteine levels were lower (curcumin before: 12.22 ± 2.29 µg/mL, after: 8.62 ± 1.02 µg/mL versus placebo before: 9.45 ± 0.84 µg/mL, after: 11.84 ± 1.63 µg/mL; P = 0.04) and high-density lipoprotein levels were higher (curcumin before: 40.77 ± 5.37 mg/dL, after: 54.56 ± 11.72 mg/dL versus placebo before: 61.20 ± 5.76 mg/dL, after: 48.82 ± 5.49 mg/dL; P = 0.04) in the curcumin group relative to the placebo group. However, there was no significant difference in changes between the circulating concentrations of glucose, insulin, leptin, adiponectin, or oxidative stress biomarkers in the curcumin group compared with the placebo group (P > 0.05). No changes were found with endothelial function, augmentation index, or central blood pressure in the curcumin group compared with the placebo group (P > 0.05). CONCLUSIONS: Our data provide evidence for an enhanced bioavailable curcumin to improve homocysteine and high-density lipoprotein concentrations, which may promote favorable cardiovascular health in young, obese men. Improvements in endothelial function or blood pressure were not observed with curcumin supplementation, thus further investigation is warranted.

Mineral bone disorders in chronic kidney disease.

As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling - scenario, which is known as CKD-mineral bone disease (MBD). CKD-MBD is characterized by : (i) abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone turnover, mineralization, volume linear growth or strength; (iii) soft-tissue calcifications, either vascular or extra-osseous. Uremic vascular calcification and osteoporosis are the most common complications related to CKD-MBD. Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism disturbed bone mineralization and makes it difficult for calcium and inorganic phosphate to enter into bone, resulting in increased serum calcium and inorganic phosphate. Vascular calcification worsens by hyperphosphatemia and systemic inflammation. Since vitamin D deficiency plays an important role in renal osteodystrophy, supplement of nutritional vitamin D is important in treating uremic osteoporosis and vascular calcification at the same time. Its pleotropic effect improves the bone remodeling initiated by osteoblast and alleviates the risk factors for vascular calcification with less hypercalcemia than vitamin D receptor analogs. Therefore, nutritional vitamin D should be considered in managing CKDMBD.

Treatment of atherosclerosis by traditional Chinese medicine: Questions and quandaries.

Atherosclerosis and its complications, such as myocardial infarction and stroke, are the major causes of morbidity and mortality, and development of effective therapies for both prevention and treatment of this disease is critically important. Currently, there are many drugs available for atherosclerotic disease, but the lipid-lowering drugs statins are still the first-choice for treatment of hypercholesterolemia, a major risk factor for atherosclerosis. On the other hand, traditional Chinese medicines, mainly Chinese herbal medicines (CHM), have been widely used in China and in other Asian countries for the treatment of atherosclerotic diseases. Although many CHMs have been reported to be effective for treating atherosclerotic diseases for more than two thousand years, there are still many difficulties for their use, such as lack of scientific evidence assessed by rigorous clinical trials, complicated components and unclear pharmacological mechanisms, which often hamper the widespread use of CHMs in Western countries. Due to these concerns, CHMs are usually considered as complimentary or alternative treatment for atherosclerotic diseases. In this review, we provide an overview of the pathophysiology of atherosclerosis viewed by Western and traditional Chinese medicine, summarize pros and cons on the efficacy of CHMs for atherosclerosis and discuss what is necessary for CHM use to spread to Western societies.

Effects of moderate exercise and a multiple vitamin and mineral complex on the arterial wall.

BACKGROUND: Aerobic exercise has favorable effects on vascular structure and function. Its beneficial role may be due to a decrease in oxidative stress. The association of vitamin and mineral supplements to exercise determined contradictory effects on arterial wall and oxidative stress parameters. The aim of this experimental study was to evaluate the effect of moderate aerobic exercise, alone or in association with a vitamin and mineral complex, on aortic wall morphology and oxidant/antioxidant balance. MATERIALS AND METHODS: Four groups, each of 10 Wistar rats, were included in the study, as follows: (I) sedentary controls, (II) group subjected to physical exercise, (III) group subjected to physical exercise and nutritional supplement, and (IV) sedentary nutritional supplemented group. Aortic wall histological examinations and serum and aortic wall oxidative stress measurements were performed in each group. RESULTS: Moderate aerobic exercise induces vascular smooth muscle cell hypertrophy and transformation in a secretory phenotype. There was a trend for increase in malondialdehyde (MDA) and decrease in thiol (SH) groups in aortic tissue homogenates, together with reduction in serum MDA values and increase in SH groups, after exercise. A reduction in aortic wall lipid peroxidation was found in supplemented trained animals compared to sedentary group, while no influence on aortic structure was noted. CONCLUSIONS: Moderate aerobic exercise induces adaptive modifications in the arterial wall and a favorable effect on systemic oxidative response. The association of vitamin and mineral supplement did not influence significantly arterial morphology, while its effects on aortic oxidative stress suggest an increase in local antioxidant defense.

Wavelength-dependence of vasodilation and NO release from S-nitrosothiols and dinitrosyl iron complexes by far red/near infrared light.

Far red/near infrared (R/NIR) energy is a novel therapy, but its mechanism of action is poorly characterized. Cytochrome c oxidase (Cco) of the mitochondrial electron transport chain is considered the primary photoacceptor for R/NIR to photolyze a putative heme nitrosyl in Cco to liberate free nitric oxide (NO). We previously observed R/NIR light directly liberates NO from nitrosylated hemoglobin and myoglobin, and recently suggested S-nitrosothiols (RSNO) and dinitrosyl iron complexes (DNIC) may be primary sources of R/NIR-mediated NO. Here we indicate R/NIR light exposure induces wavelength dependent dilation of murine facial artery, with longer wavelengths (740, and 830 nm) exhibiting reduced potency when compared to 670 nm. R/NIR also stimulated NO release from pure solutions of low molecular weight RSNO (GSNO and SNAP) and glutathione dinitrosyl iron complex (GSH-DNIC) in a power- and wavelength-dependent manner, with the greatest effect at 670 nm. NO release from SNAP using 670 was nearly ten-fold more than GSNO or GSH-DNIC, with no substantial difference in NO production at 740 nm and 830 nm. Thermal effects of irradiation on vasodilation or NO release from S-nitrosothiols and DNIC was minimal. Our results suggest 670 nm is the optimal wavelength for R/NIR treatment of certain vascular-related diseases.

Fenugreek (Trigonella Foenum-Graecum) Seed Flour and Diosgenin Preserve Endothelium-Dependent Arterial Relaxation in a Rat Model of Early-Stage Metabolic Syndrome.

Fenugreek is a common herb possessing several bioactive components including diosgenin. Here, dietary fenugreek seed flour and diosgenin were evaluated on a model of endothelium-dependent vasorelaxation by abdominal aortas isolated from rats receiving high-fat, high-sugar diet (HFHSD). 60 male Wistar rats were randomized into six groups: (i) negative control getting conventional rat feed regimen; (ii) positive control receiving HFHSD; (iii) a test group fed 2 g/kg bw/day fenugreek seed flour (containing 10 mg/kg bw/day diosgenin) + HFHSD; (iv) three test groups fed 1, 10 and 50 mg/kg bw/day diosgenin + HFHSD. Alimentary treatments were carried out for six weeks. The abdominal aortas were isolated, and 2 mm wide rings were sectioned off and mounted at a resting tension of 10 mN in organ baths containing Krebs solution (36 °C) exposed to 95% O2 and 5% CO2. After 60-min incubation, a norepinephrine concentration-response (E/c) curve was generated to determine their half-maximal effective concentration (EC50) value. After 60-min wash-out, a pre-contraction with norepinephrine EC50 was made, followed by an acetylcholine E/c curve. Plasma glutathione levels, glutathione-handling enzyme activities and blood antioxidant capacities were also determined. HFHSD significantly decreased the dilatory response to acetylcholine and increased plasma glutathione levels and these effects were significantly reversed by fenugreek seed flour, 10 and 50 mg/kg bw/day diosgenin. Both fenugreek and diosgenin treatments prevent HFHSD-induced endothelial dysfunction and redox changes. As fenugreek treatment was more effective at lower acetylcholine concentrations than diosgenin treatments, components of fenugreek other than diosgenin may contribute to the beneficial effects of dietary fenugreek seed flour.

The potential applications of mushrooms against some facets of atherosclerosis: A review.

Atherosclerosis is a complex pathology that involves several factors in its development, like oxidative stress, inflammation, hyperlipidemia, platelet aggregation and thrombus formation. Several drugs and therapeutic approaches have been developed to handle these aspects of atherosclerosis. However, some of these treatments can be costly and have undesirable side effects. Many constituents of mushrooms have been shown to have potential anti-atherosclerotic effects in several in vitro and in vivo studies. Recently, the possible mechanisms in which they exert these effects have also been elucidated. In this review, some of the research focusing on mushrooms and their potential anti-atherosclerotic effects are examined. Many mushroom species exhibited anti-oxidative, anti-inflammatory and hypolipidemic effects that can potentially attenuate the progression of atherosclerosis, either through their isolated compounds or use of crude extracts. More studies are focused on the effect that mushrooms have on gene expressions that are involved in oxidative stress, inflammation, and hyperlipidemia. These studies could provide us with a better understanding on the mechanisms in which the consumption of mushrooms could exert their possible anti-atherosclerotic effects. Further research needs to be done to uncover other possible mechanisms that are affected by mushroom use.

The acute effect of black tea consumption on resistance artery endothelial function in healthy subjects. A randomized controlled trial.

BACKGROUND & AIMS: Black tea is a main source of flavonoids in the Western diet and has been associated with reduced risk for cardiovascular disease, possibly through lowering blood pressure. These effects may be mediated through improving endothelial function of resistance arteries. The aim of this study was therefore to examine the acute impact of black tea on forearm resistance artery endothelial function in healthy, normotensive middle-aged subjects. METHODS: Twenty middle-aged men and women (age-range 45-75 years) were recruited into a double-blind, randomized, placebo-controlled crossover intervention study. Forearm resistance artery blood flow (FBF, measured using venous occlusion plethysmography) in response to incremental doses of acetylcholine, sodium nitroprusside and L-NG-monomethyl arginine were determined 2 h after consumption of either black tea containing ∼400 mg flavonoids (equivalent to 2-3 cups of tea) or a taste- and color-matched placebo. RESULTS: The mean FBF-response to acetylcholine after tea consumption was 23% higher compared to the response after placebo (95% CI: -20%, +88%), but this difference did not reach statistical significance (P = 0.32). No significant differences in the FBF-responses to sodium nitroprusside and L-NG-monomethyl arginine were found between the tea and placebo interventions (P = 0.96 and 0.74, respectively). Correcting FBF for changes in blood pressure did not alter the outcomes. CONCLUSIONS: We found no evidence that acute intake of black tea significantly altered endothelium-dependent vasodilation of forearm resistance arteries in healthy middle-aged subjects. Interventions with a longer duration of tea ingestion are required to further explore the (long-term) impact of tea flavonoids on blood pressure regulatory mechanisms. This trial was registered at clinicaltrials.gov as NCT02328339.