Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted. AIM: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors. METHODS: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias. RESULTS: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006). CONCLUSIONS: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.

The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines.

The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (- 6.45 ± 0.82 mg/dl vs - 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (- 2.02 ± 0.30 ng/ml vs - 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.

Analysis of the Increase of Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression and the Effect of Exposure in a Hyperbaric Chamber on VCAM-1 in Human Blood Serum: A Cross-Sectional Study.

Background and Objectives: Vascular cell adhesion molecule-1 (VCAM-1) was identified as a cell adhesion molecule that helps to regulate inflammation-associated vascular adhesion and the transendothelial migration of leukocytes, such as macrophages and T cells. VCAM-1 is expressed by the vascular system and can be induced by reactive oxygen species, interleukin 1 beta (IL-1ß) or tumor necrosis factor alpha (TNFα), which are produced by many cell types. The newest data suggest that VCAM-1 is associated with the progression of numerous immunological disorders, such as rheumatoid arthritis, asthma, transplant rejection and cancer. The aim of this study was to analyze the increase in VCAM-1 expression and the impact of exposure in a hyperbaric chamber to VCAM-1 levels in human blood serum. Materials and Methods: The study included 92 volunteers. Blood for the tests was taken in the morning, from the basilic vein of fasting individuals, in accordance with the applicable procedure for blood collection for morphological tests. In both groups of volunteers, blood was collected before and after exposure, in heparinized tubes to obtain plasma and hemolysate, and in clot tubes to obtain serum. The level of VCAM-1 was determined using the immunoenzymatic ELISA method. Results: The study showed that the difference between the distribution of VCAM-1 before and after exposure corresponding to diving at a depth of 30 m was at the limit of statistical significance in the divers group and that, in most people, VCAM-1 was higher after exposure. Diving to a greater depth had a much more pronounced impact on changes in VCAM-1 values, as the changes observed in the VCAM-1 level as a result of diving to a depth of 60 m were statistically highly significant (p = 0.0002). The study showed an increase in VCAM-1 in relation to the baseline value, which reached as much as 80%, i.e., VCAM-1 after diving was almost twice as high in some people. There were statistically significant differences between the results obtained after exposure to diving conditions at a depth of 60 m and the values measured for the non-divers group. The leukocyte level increased statistically after exposure to 60 m. In contrast, hemoglobin levels decreased in most divers after exposure to diving at a depth of 30 m (p = 0.0098). Conclusions: Exposure in the hyperbaric chamber had an effect on serum VCAM-1 in the divers group and non-divers group. There is a correlation between the tested morphological parameters and the VCAM-1 level before and after exposure in the divers group and the non-divers group. Exposure may result in activation of the endothelium.

Effect of pomegranate juice on vascular adhesion factors: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular diseases, obesity, and insulin resistance demonstrate elements of functional impairment of the endothelium. Treatment of endothelial dysfunction with natural products, such as pomegranate, can open new ways in the treatment of cardiovascular diseases. PURPOSE: The present meta-analysis provides information in highlighting the role of pomegranate in endothelial dysfunction. METHODS: Various databases, such as PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were searched up to July 2020 using relevant keywords. We have selected the studies that investigated the effects of pomegranate on vascular adhesion factors, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and interleukin-6 (IL-6). MD with 95% CrI with 100,000 iterations by using Markov chain Monte Carlo code were used. RESULTS: Pooled effect size of articles in human studies indicated that pomegranate juice was not significantly effective on ICAM-1 [MD: -0.42; CrI: (-1.01, 0.17)], VCAM-1 [MD: -0.20; CrI: (-1.95, 1.40)], and E-selectin [MD: -0.21; CrI: (-1.62, 1.21)] compared to the control group. But it can significantly reduce IL-6 [MD: -1.07; CrI: (-1.90, -0.19)]. CONCLUSION: Generally, present study showed that pomegranate juice has no significant effect on vascular adhesion factors, ICAM-1, VCAM-1, and E-selectin, but can reduce IL-6 significantly. Future prospective randomized clinical trials with longer intervention duration are warranted to obtain a precise conclusion.

Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial.

Inflammation and endothelial dysfunction are major problems in hemodialysis (HD) patients. This study assessed the effects of an 8 week administration of pomegranate peel extract (PPE) and vitamin E (Vit E) alone or in combination on the biomarkers of inflammation, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the biomarkers of endothelial function, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, in HD patients. In a randomized, double-blind, parallel, placebo-controlled trial, 100 HD patients were randomly divided into 4 equal groups: (a) PPE + Vit E, received 2 pomegranate tablets (each tablet contained 225 mg PPE, equal to 90 mg ellagic acid) + 1 Vit E soft gel (400 IU) daily, (b) PPE, received 2 pomegranate tablets + 1 Vit E placebo soft gel daily, (c) Vit E, received 1 Vit E soft gel + 2 pomegranate placebo tablets daily, and (d) placebo, received 2 pomegranate placebo tablets + 1 Vit E placebo soft gel daily. For group allocation, a stratified block randomization procedure based on sex, age, and HD duration was used. Each intervention product and its placebo had identical shape, color, size, and packaging. Consumption of PPE + Vit E significantly reduced the serum CRP level (mean change: -7.12 ± 4.59 mg l-1, P < 0.001) compared to other groups, while reduced levels of IL-6 (mean change: -2.19 ± 2.33 pg ml-1, P < 0.001), TNF-α (mean change: -2.41 ± 3.21 pg ml-1, P = 0.008), ICAM-1 (mean change: -64.2 ± 111.0 ng ml-1, P = 0.017), and VCAM-1 (mean change: -117.7 ± 177.1 ng ml-1, P = 0.002) were observed compared to the control. There was no significant difference in the P-selectin level among the groups. Consumption of PPE or Vit E alone significantly reduced the CRP level (mean change for PPE: -3.58 ± 5.41 mg l-1, P < 0.001; mean change for Vit E: -3.25 ± 8.29 mg l-1, P = 0.002) compared to the control. As a result, consumption of PPE in combination with Vit E enhanced the inflammatory status and endothelial function in HD patients.

Regulation of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia.

OBJECTIVE: To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia. PATIENTS AND METHODS: Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific ß1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor ß1(TGF-ß1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues. RESULTS: After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-ß1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-ß1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05). CONCLUSIONS: Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial.

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p < 0.001, median nerve; +1.60 m/s, IQR 1.80, p < 0.001, sural nerve; +0.75 m/s, IQR 2.25, p < 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

Daily watermelon consumption decreases plasma sVCAM-1 levels in overweight and obese postmenopausal women.

Postmenopausal status is associated with an increase in total and abdominal body fat as well as increased incidence of insulin resistance and cardiovascular disease. The purpose of this study was to determine if watermelon supplementation affects select systemic markers of atherosclerosis and measures of insulin resistance in overweight and obese postmenopausal women. We hypothesized that overweight and obese postmenopausal women consuming 100% watermelon puree daily for 6 weeks would have improved levels of select systemic markers connected with cardiovascular disease without changing markers of insulin resistance. To test this hypothesis, overweight and obese postmenopausal women were recruited to participate in this study. Participants were randomly assigned to either the control group (no intervention) or the watermelon puree group (WM) for 6 weeks. Plasma concentration of markers connected with atherosclerosis and glycemic control were measured pre- and poststudy. A significant 6% decrease in soluble vascular cell adhesion molecule-1 occurred pre- to poststudy in WM, P = .003. The pattern of change in fasting blood glucose (P = .633), insulin (P = .158), and homeostatic model assessment-estimated insulin resistance (P = .174) did not differ between groups. Pre- to poststudy increases were measured in the fasting plasma concentration of l-arginine (8%, P = .005), cis-lycopene (32%, P = .003), and trans-lycopene (42%, P = .003) in WM. We conclude that 6 weeks of watermelon supplementation improved soluble vascular cell adhesion molecule-1 levels, a marker connected to atherogenesis, independent of changes in body composition or glycemic control.

Effect of flaxseed supplementation on markers of inflammation and endothelial function: A systematic review and meta-analysis.

OBJECTIVES: The rationale for the current study was to evaluate the efficacy of flaxseed supplementation on important adhesion molecules and inflammatory cytokines in adults. METHODS: We conducted searches of published literature in PubMed, Scopus, Web of Science, and Google Scholar databases from inception until May 2019. All randomized controlled trials (RCTs) which investigated the effects of flaxseed supplementation on the circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion protein 1 (VCAM-1), E-selectin, and intercellular adhesion molecule 1 (ICAM-1) were included in our analysis. Results were summarized using weighted mean differences (WMDs) by random-effects model. RESULTS: Forty eligible RCTs, including 2520 participants were identified. The results of the meta-analysis revealed flaxseed supplementation reduced the concentrations of CRP (WMD = -0.387 mg/L; 95% CI: -0.653, -0.121, p = 0.004), IL-6 (WMD = -0.154 pg/Ml; 95% CI: -0.299, -0.010, p = 0.036), and VCAM-1 (WMD = -22.809 ng/ml; 95% CI: -41.498, -4.120, p = 0.017) but had no significant effect on TNF-α (WMD = -0.077 pg/mL; 95% CI: -0.317, 0.163, p = 0.530), ICAM-1 (WMD = -8.610 ng/ml; 95% CI: -21.936, 4.716, p = 0.205), and E-selectin (WMD = -1.427 ng/ml; 95% CI: -4.074, 1.22, p = 0.291). CONCLUSIONS: These findings showed that flaxseed supplementation may improve some circulating concentrations of specific adhesion molecules and inflammatory cytokines. However, well-designed trials are needed to confirm the range of non-significant and/or equivocal findings.

Policosanol Attenuates Cholesterol Synthesis via AMPK Activation in Hypercholesterolemic Rats.

This study was carried out to investigate the effects of policosanol on high-fat and high-cholesterol diet-induced hypercholesterolemic rats to provide strong evidence in support of its hypocholesterolemic effect. The hypercholesterolemic rats showed elevations in liver weight, total triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol in serum; however, policosanol supplementation reduced these markers significantly. In addition, we found that policosanol supplementation stimulated an increase in fecal cholesterol and bile acid contents and deactivated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase by AMP-activated protein kinase (AMPK) phosphorylation during high-fat and high-cholesterol-containing diet-induced development of hypercholesterolemia. Policosanol supplementation decreased ApoB levels and increased LDL-receptor expression, but it did not affect the hepatic ACAT2 level in livers from hypercholesterolemic rats. Moreover, supplementation with policosanol significantly decreased aortic wall thickness and levels of P-selectin and soluble vascular cell adhesion molecule (sVCAM-1) in serum. In conclusion, we suggest that policosanol supplementation induces antihypercholesterolemia by inhibiting cholesterol biosynthesis, LDL cholesterol uptake, and cholesterol excretion.

A randomized controlled trial to determining the effect of cinnamon on the plasma levels of soluble forms of vascular adhesion molecules in type 2 diabetes mellitus.

Soluble forms of vascular adhesion molecules, ICAM-1 and VCAM-1, accelerate atherosclerosis pathogenesis. The present study was conducted to evaluate the effect of daily supplementation of 3 g cinnamon on the plasma levels of ICAM-1 and VCAM-1 among patients with type 2 diabetes. This randomized double-blind placebo-controlled trial was performed on 44 adult patients with type 2 diabetes aged 25-70 years. The patients were randomized to two groups of intervention (n = 22) and control (n = 22), differing by daily cinnamon supplementation or placebo (3 g) for 8 weeks. Plasma levels of ICAM-1 and VCAM-1 were measured at the beginning and end of the study. After 8 weeks, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) completed the trial. There was a significant reduction in the mean levels of ICAM-1 and VCAM-1 within cinnamon and placebo groups (P < 0.001). But there was no significant difference in ICAM-1 (P = 0.75) and VCAM-1 (P = 0.72) between the groups at the end of the trial. According to the results, cinnamon supplementation has no beneficial effect on the reduction of ICAM-1 and VCAM-1 levels in patients with type 2 diabetes, which have a role in the development of atherogenesis.

Shexiang Baoxin Pill Alleviates the Atherosclerotic Lesions in Mice via Improving Inflammation Response and Inhibiting Lipid Accumulation in the Arterial Wall.

Epidemiological studies have demonstrated that cardiovascular diseases (CVDs) are the leading cause of death in the world. Atherosclerosis, a kind of chronic vascular disorder related to multiple pathogenic processes, has been reported to be an underlying cause of CVDs. Shexiang Baoxin Pill (SBP) is a traditional Chinese medicine formulation and has been broadly used for the treatment of CVDs in East Asia. However, whether SBP affects the development of atherosclerosis is poorly understood. The aim of this study was to investigate the antiatherosclerotic roles and relevant mechanisms of SBP in apolipoprotein E knockout mice. Our results showed that SBP treatment markedly decreased the size of atherosclerotic plaques of the entire aorta and the aortic sinus. Biochemical analyses indicated that SBP gavage improved oxidative stress in vivo, as seen by the level elevation of SOD, CAT, and GSH and the level reduction of MDA, H2O2, and MPO. Moreover, the concentration of MCP-1, IFN-γ, and IL-17A was reduced, and the content of IL-10 and TGF-ß1 was increased in the serum from SBP-treated mice. We discovered that the expression levels of inflammatory factors including VCAM-1, ICAM-1, IL-6, and IL-2 in the vascular wall of the SBP group were also decreased in comparison with those of the normal saline group. Moreover, we found that SBP alleviated the activation of inflammation-related pathways in the aorta tissue, as seen by the level elevation of Mfn2 and reduced phosphorylation of p38, JNK, and NF-κB. Furthermore, western blot showed that SBP administration reduced the level of SR-A and LOX-1 and elevated the content of LXRα, ABCA1, and ABCG1 in the arterial wall, indicating that SBP was capable of alleviating lipid influx and facilitating lipid efflux. In conclusion, our data suggested that SBP exerted antiatherosclerotic effects via improving inflammation response and inhibiting lipid accumulation.

Antiatherosclerotic Properties of Echinodorus grandiflorus (Cham. & Schltdl.) Micheli: From Antioxidant and Lipid-Lowering Effects to an Anti-Inflammatory Role.

Echinodorus grandiflorus is an important medicinal plant species that is native to South America. Despite extensive popular usage as a hypolipidemic drug, its effects as an atheroprotective agent remain unknown. The aim of this study was to evaluate the effects of an ethanol-soluble fraction that was obtained from E. grandiflorus (ESEG) leaves against the development of atherosclerosis in rabbits. Male rabbits received a diet that was supplemented with 1% cholesterol (cholesterol-rich diet [CRD]) for 60 days. After 30 days of the CRD, the animals were divided into five groups (n = 6) and treated with ESEG (10, 30, and 100 mg/kg), simvastatin (2.5 mg/kg), or vehicle once daily for 30 days. The negative control group was fed a cholesterol-free diet and treated orally with vehicle. At the end of 60 days, serum lipids, oxidized low-density lipoprotein, thiobarbituric acid reactive substances, nitrotyrosine, and serum interleukin 1 beta (IL-1ß), IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were determined. Samples from the aortic arch and thoracic segment were also collected to investigate the tissue antioxidant defense system and perform histopathological analysis. Oral ESEG administration significantly reduced serum lipid levels in CRD-fed rabbits. This treatment also modulated the arterial antioxidant defense system by reducing lipid and protein oxidation. Similarly, serum IL-1ß, IL-6, sICAM-1, and sVCAM-1 levels significantly decreased, accompanied by a reduction of atherosclerotic lesions in all arterial branches. These findings suggest that ESEG may be a new herbal medicine that can be directly applied for the treatment and prevention of atherosclerotic disease.

Spirulina maxima Decreases Endothelial Damage and Oxidative Stress Indicators in Patients with Systemic Arterial Hypertension: Results from Exploratory Controlled Clinical Trial.

(1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such as being anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. (2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension (SAH) undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive substances, were also quantified before and after the treatment period. (3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. (4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.

Anti-atherosclerosis of oligomeric proanthocyanidins from Rhodiola rosea on rat model via hypolipemic, antioxidant, anti-inflammatory activities together with regulation of endothelial function.

BACKGROUND: Rhodiola rosea has been used as a traditional medicine for a long history. Previous studies on oligomeric proanthocyanidins from Rhodiola rosea (OPCRR) have showed that it exhibited significant free radical-scavenging activities, antioxidant activities in aging mice and lipid lowering effects. HYPOTHESIS/PURPOSE: We hypothesized that OPCRR can improve the atherosclerosis pathological in rats. In the present study, we investigated the effects of OPCRR on the serum lipid profiles, oxidant stress status, inflammatory cytokines and atherosclerotic mediators, and endothelial dysfunction as well as changes in abdominal aorta of atherosclerosis rats. METHODS: The major components of OPCRR were analyzed by using infrared spectrum and HPLC-ESI-MS. The atherosclerosis rat model was induced by high fat and vitamin D3 feeding for 9 weeks and two OPCRR doses (60 and 120 mg/kg b.w.) were orally administered daily for 9 weeks. The rats were then sacrificed and the blood was collected via abdominal aorta and serum was separated by centrifugated for biochemical analysis. Part of the aorta tissues were excised immediately for histopathological examination and western blotting. RESULTS: Compared to model group, OPCRR treatments significantly decreased the serum lipid profiles including total cholesterol, total triglycerides, low-density lipoprotein cholesterol (LDL-C) and ox-LDL and increased the high-density lipoprotein cholesterol (HDL-C); significant increased serum antioxidant enzymes (SOD and GSH-Px) and decrease of MDA content as a product of lipid peroxidation; lowered serum levels of TNF-α, IL-1ß, IL-6, ICAM-1 and VCAM-1 and enhanced IL-10 level; increased the serum release of nitric oxide and expression of iNOS in aortic, whereas decreased the expression of eNOS. CONCLUSION: OPCRR can improve the progress of atherosclerosis by regulation of lipid metabolism, restoring of the antioxidant capacities, and attenuation of pro-inflammatory cytokines and chemcytokines release, and improving the endothelial dysfunction indicated by nitric oxide system.

Differential responses of endothelial integrity upon the intake of microencapsulated garlic, tomato extract or a mixture: a single-intake, randomized, double-blind, placebo-controlled crossover trial.

This study investigated the effect of microencapsulated garlic and/or tomato on endothelial dysfunction induced by the PhenFlex test (PFT) in healthy male smokers. In a randomized, double-blind, placebo-controlled crossover trial, 41 healthy male smokers were randomly assigned to one of four groups to receive the test groups (in microencapsulated garlic powder, tomato extract and a mixture thereof) or the placebo group. Proteomic biomarkers related to endothelial integrity were measured in plasma. Microencapsulated garlic, tomato extract and the mixture affected endothelial integrity biomarkers differently. Garlic consumption increased prothrombin time and decreased SAA and IL-12. Tomato extract intake increased activated partial thrombin time and decreased d-dimer, SAA, sVCAM-1, IL-13 and MCP-3 levels. Consumption of the mixture increased sE-selectin and lowered D-dimer, SAA, IL-13 and IL-10 responses after PFT challenge for 6 h. The different responses became clearer under high compliance in the dietary restriction groups. This single-intake clinical trial addressed the different responses of biomarkers related to endothelial integrity.

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease.

PURPOSE: Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients. MATERIALS AND METHODS: Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied. RESULTS: There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (ß = - 0.548, P < 0.001) and lower levels of 25(OH)D (ß = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001). CONCLUSIONS: Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

The Beneficial Radioprotective Effect of Tomato Seed Oil Against Gamma Radiation-Induced Damage in Male Rats.

Radiation protection research receives intense focus due to its significant impact on human health. The present study was undertaken to investigate the protective effect of pretreatment with tomato seed oil (TSO) against gamma radiation-induced damage in rats. Male Wistar rats were divided into four groups: (1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO-pretreated and gamma-irradiated. Acute exposure of animals to a single gamma radiation dose (6 Gy) induced oxidative stress in major body organs, altered serum lipid homeostasis, significantly increased serum testosterone and sorbitol dehydrogenase levels, and elicited a systemic inflammation as manifested by the induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO (1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected rats against ionizing radiation-induced oxidative stress, restored lipid homeostasis, and suppressed systemic inflammation. Histological findings of target tissues verified biochemical data. The radioprotective ability of TSO was attributed to its content of phytosterols, policosanol, and antioxidants, including lycopene, ß-carotene, lutein, and tocopherols. TSO is considered a promising radioprotective agent that can be effectively used to protect the body from the damaging effects of harmful radiation.

Effect of dietary alpha-linolenic acid on blood inflammatory markers: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The aim of the current meta-analysis was to investigate the effect of increasing dietary ALA intake on the blood concentration of inflammatory markers including tumor necrosis factor (TNF), interleukin 6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in adults. METHODS: After a systemic search on PubMed, Embase, and Cochrane library and bibliographies of relevant articles, 25 randomized controlled trials that met the inclusion criteria were identified. RESULTS: No significant effect of dietary ALA supplementation was observed on TNF (SMD: -0.03, 95% CI -0.36 to 0.29), IL-6 (SMD: -0.17, 95% CI -0.46 to 0.12), CRP (SMD: -0.06, 95% CI -0.24 to 0.12), sICAM-1 (SMD: -0.06, 95% CI -0.26 to 0.13), and sVCAM-1 (SMD: -0.24, 95% CI -0.56 to 0.09). Subgroup analysis revealed that increasing dietary ALA tends to elevate CRP concentration in healthy subjects. However, the null effect of ALA supplementation on other inflammatory markers was not changed in various subgroups, indicating that the results are stable. Meta-regression results revealed a negative relationship between the effect size on CRP and its baseline concentration. No significant publication bias was observed for all inflammatory markers as suggested by funnel plot and Begg's test. CONCLUSION: Our meta-analysis did not find any beneficial effect of ALA supplementation on reducing inflammatory markers including TNF, IL-6, CRP, sICAM-1, and sVCAM-1. However, in healthy subjects, ALA supplementation might increase CRP concentration.

Changes in blood pressure, vascular reactivity and inflammatory biomarkers following consumption of heated corn oil.

Consumption of corn oil for cooking purpose is gaining popularity. The present study examined the effect of heated corn oil on blood pressure and its possible mechanism in experimental rats. Thirty male Sprague-Dawley rats were randomly divided into 5 groups and were fed with the following diets, Group I was fed with basal diet only; whereas group II,III,IV and V were fed with basal diet fortified with 15% (w/w) either fresh, once-heated, five-times-heated or ten-times-heated corn oil, respectively for 16 weeks. Body weight, blood pressure were measured at baseline and weekly interval for 16 weeks. Inflammatory biomarkers which included soluble intracellular adhesion molecules (sICAM), soluble vascular adhesion molecules (sVCAM) and C reactive protein (CRP), were measured at baseline and the end of 16 weeks. The rats were sacrificed and thoracic aorta was taken for measurement of vascular reactivity. There was significant increase in the blood pressure in the groups fed with heated once, five-times (5HCO) and ten-times-heated corn oil (10-HCO) compared to the control. The increase in the blood pressure was associated with an increase in CRP, sICAM and sVCAM, reduction in vasodilatation response to acetylcholine and greater vasoconstriction response to phenylephrine. The results suggest that repeatedly heated corn oil causes elevation in blood pressure, vascular inflammation which impairs vascular reactivity thereby predisposing to hypertension. There is a need to educate people not to consume corn oil in a heated state.