Chokeberry Juice Containing Polyphenols Does Not Affect Cholesterol or Blood Pressure but Modifies the Composition of Plasma Phospholipids Fatty Acids in Individuals at Cardiovascular Risk.

Chokeberry polyphenols have been suggested to reduce cholesterol and blood pressure and thus protect against cardiovascular diseases (CVD), but the evidence in humans is limited and inconsistent. This randomized double-blinded three-parallel groups trial investigated the changes in various anthropometric and clinical biomarkers, and in plasma phospholipids fatty acids (PPFA) in volunteers at cardiovascular risk after a four-week intervention with 100 mL/day of (1) chokeberry juice with a high-dose of polyphenols (1177.11 mg gallic acid equivalents, GAE); (2) chokeberry juice with a low-dose of polyphenols (294.28 mg GAE) and; (3) a nutritionally matched polyphenol-free placebo drink. Our results indicate that the intake of chokeberry juice containing either the low or the high dose of polyphenols cannot be linked with a reduction in total- and low-density lipoprotein (LDL)cholesterol or in systolic (SBP) and diastolic (DBP) blood pressure in comparison with the consumption of the placebo drink. However, we found evidence of moderate changes in the PPFA, i.e., increased saturated fatty acids (SFA), mostly palmitic acid, and reduced n-6 polyunsaturated fatty acids (PUFA), principally linoleic acid (LA) with the intake of chokeberry against the placebo. These effects may be associated with the polyphenols but we could not differentiate a clear dose-response effect. Further research is still needed to elucidate the contribution of the polyphenolic fraction to the potential cardiovascular effects of the chokeberry and to build up the evidence of its potential benefit via the modulation of PPFA composition.

Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells.

Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells. We report that cotreatment of MCF7 with Viscum album and Dox abrogates G2/M cycle arrest replacing senescence with intrinsic apoptotic program. Mechanistically, this switch was associated with down-regulation of p21, p53/p73 as well as Erk1/2 and p38 activation. Our findings, therefore, identify a novel mechanistic axis of additive antitumor activity of Viscum album and low dose-Dox. In conclusion, ER + breast cancer patients may benefit from addition of Viscum album to low-dose Dox chemotherapy due to suppression of cancer cell senescence and induction of apoptosis.

Design, formulation and sensory evaluation of a polyphenol-rich food placebo: an example of aronia juice for food intervention studies.

Products suitable for use as controls in food interventions designed to demonstrate the role of minor components are largely lacking. In the present study, we aimed to develop a formulation to be used as a placebo in a clinical trial designed to assess the effects of aronia juice polyphenols on platelet function. Three formulations with the same nutrient composition as aronia juice were prepared by mixing various nutrients, artificial colours and flavours with water. The similarity of formulations to aronia juice in terms of taste, colour, smell and texture was assessed by six food panellists. The final placebo was tested for its impact on platelet function, biochemical and anthropometric parameters in a 4-week long study. No significant changes in platelet function, or in several cardiovascular and safety markers were recorded. Formulation suitable for use as a placebo for dietary intervention studies using aronia juice has been developed and demonstrated to be well tolerated in humans.

Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats.

This study aimed to investigate effects of citrus flavanones naringenin (NAR) and hesperetin (HES) on liver antioxidant status and membrane phospholipid composition in 24-month-old rats. NAR and HES (15mg/kg) were administrated orally to male Wistar rats, once per day, for 4weeks. Control group received either vehicle (sunflower oil) or remained intact. The results showed decreased (p<0.05) activity of antioxidant enzymes (AOE), specifically catalase (CAT), superoxide dismutase (SOD) 1 and glutathione reductase (GR) in the liver of intact control old-aged rats in comparison to young intact controls. Flavanone administration to old-aged males increased (p<0.05) examined AOE activities in comparison to vehicle-administered animals. Namely, NAR was more potent in comparison to HES regarding the increase (p<0.05) in activities of examined antioxidant enzymes (SOD 1 and 2, glutathione peroxidase-GPx and GR) and the liver glutathione (GSH), while HES elevated (p<0.05) only activity of CAT and GR. Both flavanones significantly decreased (p<0.05) TBARS and improved (p<0.05) membrane phospholipid composition in favor of n-3 PUFA and n-6/n-3 PUFA ratio. Both flavanones did not affect liver histology and reduced (p<0.05) alanine aminotransferase and aspartate aminotransferase levels in serum. The results of this study indicate beneficial potential of citrus flavanones in the old-aged rat liver.

Sensitization of K562 Leukemia Cells to Doxorubicin by the Viscum album Extract.

Toxicity of conventional chemotherapeutics highlights the requirement for complementary or alternative medicines that would reduce side effects and improve their anticancer effectiveness. European mistletoe (Viscum album) has long been used as a complementary and alternative medicine supporting cancer therapy. The aim of this study was to investigate synergistic antitumor action of V. album extract and doxorubicin during co-treatment of chemoresistant chronic myelogenic leukemia K562 cells. Combined treatment of leukemia cells led to inhibitory synergism at sub-apoptotic doxorubicin concentrations and multifold reduction of cytotoxic effects in healthy control cells. Prolonged co-treatment was associated with reduced G2/M accumulation and increased expression of early and late apoptotic markers. Our data indicate that V. album extract increases antileukemic effectiveness of doxorubicin against resistant K562 cells by preventing G2/M arrest and inducing apoptosis.

Acute effects of black currant consumption on salivary flow rate and secretion rate of salivary immunoglobulin a in healthy smokers.

The role of saliva in maintaining oral health and homeostasis is based on its physicochemical properties and biological activities of its components, including salivary immunoglobulin A (IgA). Both salivary rates and immunological status of saliva are found to be compromised in smokers. The aim of this study was to investigate the acute time-dependent effect of smoking and black currant consumption on the salivary flow rate (SFR) and salivary IgA secretion rate (sIgA SR) in healthy smokers. SFR, sIgA levels in saliva, and sIgA SRs were determined in healthy smokers (n=8) at eight times of assessment within three consecutive interventions: at the baseline; 5, 30, and 60 min after smoking; 5, 30, and 60 min after black currant consumption (100 g), followed by smoking; and 5 min after black currant consumption. Smoking induced a significant delayed effect on SFR measured 60 min after smoking (P=.03), while black currant consumption preceding smoking prevented that effect. Salivary IgA concentrations and sIgA flow rates were not acutely influenced by smoking. Black currant consumption preceding smoking induced a significant decrease in sIgA concentrations 5 min after the intervention compared with the baseline (P=.046), with a further increasing trend, statistically significant, 60 min after the intervention (P=.025). Although smoking cessation is the most important strategy in the prevention of chronic diseases, the obtained results suggest that the influence of black currant consumption on negative effects of tobacco smoke on salivary flow and immunological status of saliva could partly reduce the smoking-associated risk on oral health.

Effects of polyphenol-rich chokeberry juice on antioxidant/pro-oxidant status in healthy subjects.

Berry fruits are a rich source of polyphenols, especially anthocyanins: well-known potent anti-oxidant phytochemicals. The purpose of this study was to evaluate beneficial effects of long-term consumption of polyphenol-rich organic chokeberry juice on different markers of antioxidant/pro-oxidant status in healthy female volunteers. Twenty-nine women, aged 25-49, were included in the study. Serological markers of oxidative stress and antioxidant defence, blood pressure, routine biochemical, and anthropometric parameters were analyzed at baseline and after twelve weeks of regular chokeberry juice consumption. Significant decrease in thiobarbituric acid-reactive substances level (TBARS; P<.001) and pro-oxidant-antioxidant balance (PAB; P<.05), as well as increase in paroxonase-1 activity toward diazoxon (P<.01) were found. Total oxidative status and sulphydryl groups levels were not significantly influenced by the intervention. Anthropometric, biochemical parameters, and blood pressure values were within the referent values for all subjects and were not influenced by the chokeberry juice consumption. However, we found positive correlation between age, body mass index, waist circumference, body fat percent, blood pressure, and analyzed marker of lipid peroxidation, which was influenced by the consumption. In conclusion, the fine modulation of several antioxidant/pro-oxidant status biomarkers observed in healthy subjects indicates putative prophylactic effects of polyphenol-rich chokeberry juice and supports its importance as part of an optimal diet.

Dietary supplementation with polyphenol-rich chokeberry juice improves skin morphology in cellulite.

The aim of our study was to investigate possible beneficial effects of organic chokeberry juice (OCJ) consumption in the treatment of cellulite. Twenty-nine women aged 25-48 with a cellulite grade 2 according to the Nurnberger-Muller scale were included. Anthropometric and biochemical parameters were measured. Skin structure was analyzed by ultrasonography. All subjects consumed 100 mL of OCJ per day, during 90 days. Measurements of investigated parameters were performed at 0, 45, and 90 days of the study. A marked reduction in the subcutaneous tissue thickness was observed in all subjects, with the average reduction of 1.9 mm. The length of subcutaneous tissue fascicles (ScTFL) was reduced in 97% (28 out of 29) of subjects, with the average value of 1.18 mm. After 45 days of chokeberry juice consumption, reduction of edema was observed in 55.2% of the subjects with edema at the baseline, while at the endpoint of the study, edemas were not observed in any of the subjects involved in the study. OCJ could have beneficial effects on the cellulite condition, including the length of ScTFL, subcutaneous tissue, and dermis thickness as well as on edema reduction.

Effects of glucomannan-enriched, aronia juice-based supplement on cellular antioxidant enzymes and membrane lipid status in subjects with abdominal obesity.

The aim of this study was to analyze the effects of a 4-week-long consumption of glucomannan-enriched, aronia juice-based supplement on anthropometric parameters, membrane fatty acid profile, and status of antioxidant enzymes in erythrocytes obtained from postmenopausal women with abdominal obesity. Twenty women aged 45-65 with a mean body mass index (BMI) of 36.1 ± 4.4 kg/m(2) and waist circumference of 104.8 ± 10.1 cm were enrolled. Participants were instructed to consume 100 mL of supplement per day as part of their regular diet. A significant increase in the content of n-3 (P < 0.05) polyunsaturated fatty acids in membrane phospholipids was observed, with a marked increase in the level of docosahexaenoic fatty acid (P < 0.05). Accordingly, a decrease in the n-6 and n-3 fatty acids ratio was observed (P < 0.05). The observed effects were accompanied with an increase in glutathione peroxidase activity (P < 0.05). Values for BMI (P < 0.001), waist circumference (P < 0.001), and systolic blood pressure (P < 0.05) were significantly lower after the intervention. The obtained results indicate a positive impact of tested supplement on cellular oxidative damage, blood pressure, and anthropometric indices of obesity.

Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and aggregation.

BACKGROUND: The beneficial effect of fruit- and vegetable-rich diets on cardiovascular health is partly attributed to the effect of their bioactive compounds on platelet function. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples from healthy subjects (n = 4) and subjects with metabolic syndrome (n = 4) were treated with six extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Markers of arachidonic acid induced platelet activation and platelet-leucocyte aggregation were assessed using flow cytometry. RESULTS: In subjects with metabolic syndrome, kale extract significantly inhibited agonist induced P-selectin expression (P = 0.004). Sulforaphane-cysteine-glycine, a human plasma metabolite of the related glucosinolate, glucoraphanin, significantly inhibited P-selectin and GPIIb-IIIa expression (P = 0.020 and 0.024, respectively) and platelet-neutrophil aggregation (P = 0.027). Additionally, pomegranate extract significantly inhibited GPIIb-IIIa expression (P = 0.046) in subjects with metabolic syndrome. In healthy subjects only dill extract significantly inhibited agonist induced P-selectin expression (P = 0.025). CONCLUSION: These data show that bioactive-rich extracts of kale and pomegranate that are consumed as traditional plant foods of Black Sea area countries were effective in modulating platelet function.

Bioactive-rich extracts of persimmon, but not nettle, Sideritis, dill or kale, increase eNOS activation and NO bioavailability and decrease endothelin-1 secretion by human vascular endothelial cells.

BACKGROUND: There is increasing evidence that consumption of plant bioactives such as polyphenols and glucosinolates reduces cardiovascular disease risk and improves endothelial function. In the Black Sea area, a number of plants are consumed alone and as ingredients in traditional foods, and dill, nettle, kale, Sideritis and persimmon were identified as bioactive-rich traditional food plants. The present study investigated the effects of plant extracts on cellular markers of endothelial function (eNOS activation and expression and ET-1 secretion). RESULTS: Treatment of human umbilical vein endothelial cells with persimmon extract significantly increased Akt and eNOS phosphorylation and nitric oxide metabolites and significantly decreased secretion of ET-1 to the media after 24 h compared with a vehicle control (all P < 0.01). None of the other plant extracts significantly altered any markers of endothelial function. CONCLUSION: These findings suggest that persimmon fruit contains bioactives that can improve endothelial function via activation of eNOS and reduction in ET-1 secretion, but that dill, kale, Sideritis and nettle do not.

Lack of effect of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on platelet function.

BACKGROUND: The health benefits of fruit and vegetable-rich diets may be partly due to modulation of platelet activity by bioactive phytochemicals. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples (n =15 subjects) were treated with extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Platelet function was assessed using the PFA-100. RESULTS: None of the extracts containing various flavonoids, glucosinolates and other bioactives, or isolated bioactive metabolites of quercetin or sulforaphane, caused significant changes in PFA-100 closure time (CT). In contrast, the positive controls (aspirin and Abciximab) consistently caused significant increases in CT for the platelet agonists epinephrine and ADP, respectively. CONCLUSION: These data do not support the notion that these plant bioactives can improve human platelet function.

Bioactive-rich Sideritis scardica tea (mountain tea) is as potent as Camellia sinensis tea at inducing cellular antioxidant defences and preventing oxidative stress.

BACKGROUND: In several countries, tea (hot-water infusions of dried Camellia sinensis (CS) leaves) is a major source of antioxidant flavonoids, and its consumption has been associated with several favourable outcomes. Other plants used for the preparation of herbal teas are sources of phenolic antioxidant compounds; among them Sideritis scardica (SS) is used for the preparation of a popular drink throughout Eastern and Central Europe. We have compared the effects of an SS extract to a CS extract in HepG2 cells to set the scientific basis for the exploitation of other herbal teas in counteraction of oxidative stress. RESULTS: Although SS extract had a lower phenolic concentration and total antioxidant capacity than CS extract, their cellular antioxidant effects were similar. The different phenolic pattern of the extracts suggests that the protective activity is not limited to catechins. CONCLUSION: Although further research is needed, our data represent a first contribution for the evaluation of the potential effect of SS in increasing antioxidant defences. © 2013 Society of Chemical Industry.

Cytotoxic and cell cycle effects induced by two herbal extracts on human cervix carcinoma and human breast cancer cell lines.

In recent times interest has increased in the complementary medicine of cancer patients. Two herbal mixtures were prepared from 17 and 12 plants, respectively. The goal of this study was to examine the in vitro cytotoxic and cell cycle effects of the aqueous-ethanol extracts (Extract 1 and Extract 2) obtained by maceration of the mixtures. The two extracts investigated exhibited significant antiproliferative activity toward two human breast cancer cell lines (MDA-MB-361 and MDA-MB-453) and a human cervix carcinoma cell line (HeLa) with 50% inhibitory concentration (IC(50)) values ranging from 9.92 to 17.38 microL/mL. The extracts did not exert any significant cytotoxicity toward healthy human peripheral blood mononuclear cells. In vitro antitumor activities were accompanied by an important apoptotic fraction of all cell lines after treatment with the extracts. The amount of total phenols was similar in both extracts, whereas the concentration of total tannins was significantly higher in Extract 1. Extract 1 was also found to be a stronger free radical scavenger, with an IC(50) value of 13.4 microg/mL. Both extracts contained rosmarinic acid, while ursolic acid was identified in Extract 2.

The dry plant extract of common bean seed (Phaseoli vulgari pericarpium) does not have an affect on postprandial glycemia in healthy human subject.

The aim of present study was to assess the effects and safety of a dry Phaseoli vulgari pericarpium (PVP) extract on postprandial glycemia in healthy participants. A randomized crossover experiment where participants received either PVP extract or placebo. Chemical compounds in dry extract were assessed by established methods. Eighteen healthy participants (9 male and 9 female) aged 29+/-4,8 years, body mass index (BMI) 23+/-3,7 kg/m(2) were recruited among students and staff at the Faculty of Pharmacy, University of Belgrade. All participants were able to follow the study protocol without difficulty. The participants received either PVP extract or placebo 30 minutes before a 50g oral glucose tolerance test (OGTT). The protocol followed the guidelines for the OGTT with blood samples drawn at 0, 15, 30, 60, 90 and 120 min. This study demonstrated that there was no significantly effect of the PVP extract on incremental blood glucose (IBG) and their areas under the curve (AUC) neither male nor female participants. However, IBG together with AUC changes were significantly lower in male compared with female participants in treated and untreated groups. The presence of chrome, soluble fiber, vitamin C, protein, glucose and lectins were also quantified. The applied amount of PVP extract was unable to produce the postprandial hypoglycemia. We assumed that amounts of chrome, soluble fiber, vitamin C which have beneficial effects on diabetes treatment were sufficient to produce hypoglycemia.