Chokeberry Extract Research Articles

Role of Complementary and Alternative Medicine in Cardiovascular Diseases

Role of Complementary and Alternative Medicine in Cardiovascular Diseases

Chemotherapy modulates the biological activity of breast cancer patients plasma: The protective properties of black chokeberry extract

In breast cancer patients (before and during anti-cancer therapy) oxidative/nitrative damage to various molecules is observed. Furthermore, anti-cancer treatments may also influence the hemostatic properties of blood platelets and plasma. The aim of our study was to assess the effect of oxidative/nitrative stress (estimated by measurements of the levels of carbonyl groups and 3-nitrotyrosine in proteins – ELISA and C-ELISA methods, respectively; lipid peroxidation and total antioxidant level – TAS) on the selected parameters of hemostatic activity of plasma (the process of fibrin polymerization and lysis) collected from breast cancer patients after surgery and after various phases of chemotherapy (doxorubicin and cyclophosphamide). Subsequently, we also evaluated the level of oxidative/nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa (Aronox®) in vitro. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland. We observed increased levels of biomarkers of oxidative/nitrative stress in plasma from patients with breast cancer (before or after surgery and after various phases of chemotherapy) in comparison to healthy group. Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers. We also recognize the existence of a relationship between oxidative stress (measured by the level of carbonyl groups) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy. Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative/nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy. Considering the data presented in this study, we suggest that the oxidative/nitrative stress in plasma obtained from breast cancer patients (not only before or after the surgery, but also after various phases of doxorubicin and cyclophosphamide chemotherapy) may induce changes of hemostatic activity, which may contribute to thrombosis in these patients. Our results also suggest that the commercial extract of A. melanocarpa may be regarded as a promising new source of bioactive antioxidant natural compounds for breast cancer patients.

Induction of apoptosis and reduction of MMP gene expression in the U373 cell line by polyphenolics in Aronia melanocarpa and by curcumin

Malignant brain tumours are rare but are the most challenging types of cancers to treat. Despite conventional multimodality approaches available for their management, the outlook for most patients remains dismal due to the ability of the tumour cells to invade the normal brain. Attention has now focused on novel therapeutic interventions such as as the use of micronutrients. Both chokeberry extract (Aronia melanocarpa), which is rich in natural pigments such as anthocyanins and curcumin (diferuloylmethane) found in turmeric (Curcuma longa) have been reported to possess anticancer properties in other cancers. The aim of this study was to extend our previous research to evaluate the therapeutic potential of these two agents by testing their ability to induce apoptosis in an established glioblastoma cell line (U373). This was accomplished by treating the cells for 48h with either chokeberry extract or curcumin, and using the Annexin-V assay. Gene profiles of 8 MMPs (2, 9, 14, 15, 16, 17, 24 and 25) and 4 TIMPs (1, 2, 3 and 4) were analysed for effects of mediators of invasion by quantitative real-time polymerase chain reaction (RT-PCR). The IC50 values determined for curcumin and chokeberry extract were 15 and 200µg/ml, respectively. Our results also suggest that curcumin induces apoptosis but chokeberry extract is necrotic to this cell line. It is possible that chokeberry extract kills the cells by other non-apoptotic pathways. In addition, the RT-PCR results show downregulation of the gene expression of MMP-2, -14, -16 and -17 for both micronutrients. Taken together, the comparative data suggest that both curcumin and chokeberry extract may exhibit their anticancer potential by inducing apoptosis and inhibiting invasion by reducing MMP gene expression.

Antioxidant Activities of Chokeberry Extracts and the Cytotoxic Action of Their Anthocyanin Fraction on HeLa Human Cervical Tumor Cells

The present study evaluates the antioxidant activity of two Aronia melanocarpa cultivars-Viking and Aron-and of Aronia prunifolia hybrid in relationship with their phytochemical composition regarding the contents of total phenolics, flavonoids, procyanidins, and monomeric anthocyanins. The antioxidant capacity of the mentioned extracts of chokeberries was evaluated through five complementary assays: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), H(2)O(2) scavenging potential, oxygen radical absorbance capacity, ferric reducing antioxidant power, and cupric ion reducing antioxidant capacity. A. prunifolia hybrid was found to have the highest antioxidant activity and to be the richest in polyphenols, procyanidins, and anthocyanins compared with the A. melanocarpa cultivars. A good correlation was observed between antioxidant activity and total procyanidin and anthocyanin content. Cyanidin glycosides inhibited HeLa human cervical tumor cell proliferation and increased generation of reactive oxygen species after 48 h of treatment, suggesting that they could be responsible for the antiproliferative activity. These results may be significant for industry concerning food quality and disease prevention.

Polyphenol‐rich Aronia melanocarpa (chokeberry) extract regulates expression of cholesterol and lipid metabolism genes in Caco‐2 cells

Chokeberry, Aoronia melanocarpa, is a rich source of polyphenols. We investigated the effect of an anthocyanin‐rich chokeberry extract (CBE) on the expression of genes involved in intestinal lipid metabolism in Caco‐2 cells, a human intestinal cell line. CBE had a Total Phenols value of 745 mg gallic acid equivalents/g and contained 12% anthocyanins. Cells were incubated with 50 or 100 μg/mL of CBE for 24 h and gene expression was measured by quantitative realtime PCR. ATP binding cassette transporter (ABC) A1, scavenger receptor class B, type 1, Niemann‐Pick C1 Like 1, and HMG‐CoA reductase mRNA abundance was significantly reduced by CBE. In contrast, CBE induced LDL receptor (LDLR) and ABCG8 to levels 2.5‐ and 1.5‐fold of controls. Western blot analysis confirmed increased LDLR protein level. Expression of genes involved in lipid metabolism and chylomicron assembly, including sterol regulatory element binding protein 1c, fatty acid synthase, and acyl‐CoA oxidase and microsomal triglyceride transfer protein, was significantly decreased by CBE in a dose‐dependent manner. Our data suggest that CBE may play an important role in the flux of cholesterol as well as lipid metabolism in the intestine. Supported by College of Agriculture and Natural Resources and Research Foundation at the University of Connecticut.Grant Funding Source : College of Agriculture and Natural Resources and Research Foundation at the University of Connecticut.

Aronia melanocarpa (chokeberry) polyphenol rich extract reduces plasma cholesterol and improves antioxidant function in Apolipoprotien E knockout mice

The objective of this work was to evaluate the effect of polyphenol‐rich chokeberry extract (CBE) on lipid metabolism and antioxidant function in a mouse model for atherosclerosis. Male apoE−/− mice were fed a high fat/high cholesterol diet (15% fat, 0.2% cholesterol by wt) supplemented with 0.005% or 0.05% of CBE by wt for 4 weeks (n = 10/group). The 0.05% CBE diet provided daily doses of 0.19 mg anthocyanins, 0.17 mg phenolic acids, 0.06 mg proanthocyanidins, and 0.02 mg flavonoids. Mice consuming 0.05% CBE had ~20% lower plasma total cholesterol concentrations compared with control, without altering triglyceride levels. Despite the hypercholesterolemic effect of CBE, mRNA levels of low‐density lipoprotein receptor and HMG‐CoA reductase in CBE‐fed mice were not significantly different from controls. Dietary CBE did not alter hepatic lipids or expression of genes involved in lipogenesis and fatty acid β‐oxidation. Dietary 0.05% CBE increased plasma paraoxonase‐1 (PON1) activity 39%, but did not affect glutathione peroxidase and superoxide dismutase activities. Thus, dietary CBE improves antioxidant function and its cholesterol‐lowering effect may be independent of hepatic cholesterol metabolism. Supported by College of Agriculture and Natural Resources and Research Foundation at the University of Connecticut.

An extract of chokeberry attenuates weight gain and modulates insulin, adipogenic and inflammatory signalling pathways in epididymal adipose tissue of rats fed a fructose-rich diet

Chokeberries are a rich source of anthocyanins, which may contribute to the prevention of obesity and the metabolic syndrome. The aim of the present study was to determine if an extract from chokeberries would reduce weight gain in rats fed a fructose-rich diet (FRD) and to explore the potential mechanisms related to insulin signalling, adipogenesis and inflammatory-related pathways. Wistar rats were fed a FRD for 6 weeks to induce insulin resistance, with or without chokeberry extract (CBE) added to the drinking-water (100 and 200 mg/kg body weight, daily: CBE100 and CBE200). Both doses of CBE consumption lowered epididymal fat, blood glucose, TAG, cholesterol and LDL-cholesterol. CBE consumption also elevated plasma adiponectin levels and inhibited plasma TNF-α and IL6, compared with the control group. There were increases in the mRNA expression for Irs1, Irs2, Pi3k, Glut1, Glut4 and Gys1, and decreases in mRNA levels of Gsk3β. The protein and gene expression of adiponectin and Pparγ mRNA levels were up-regulated and Fabp4, Fas and Lpl mRNA levels were inhibited. The levels of gene expression of inflammatory cytokines, such as Il1β, Il6 and Tnfα were lowered, and protein and gene expression of ZFP36 (zinc finger protein) were enhanced in the epididymal adipose tissue of the rats that consumed the CBE200 extract. In summary, these results suggest that the CBE decreased risk factors related to insulin resistance by modulating multiple pathways associated with insulin signalling, adipogenesis and inflammation.

Solid-phase extraction of berries’ anthocyanins and evaluation of their antioxidative properties

Solid-phase extraction (SPE) was used to obtain anthocyanin-rich extracts from five berry species: chokeberry, elderberry, black currant, blackberry and blueberry. During SPE more than 94.4% of the sugars and more than 88.5% of the acids present in the crude extracts were separated. The SPE resulted in 90–95.6% anthocyanins recovery. The antioxidative properties of the anthocyanin-rich extracts were tested by measuring their oxygen radical absorption capacity (ORAC), hydroxyl radical averting capacity (HORAC), total peroxyl radical trapping antioxidant parameter (TRAP), scavenging of nitric oxide and inhibition of lipid peroxidation. Elderberry extract revealed the highest ORAC value of 5783 μmol TE/g. Chokeberry extract was the most potent inhibitor of lipid peroxidation and had the highest TRAP value of 4051 μmol TE/g. Blueberry extract had the highest HORAC result – 1293 μmol GAE/g and was the most powerful scavenger of NO. The high antioxidant activity according to all antioxidant assays revealed opportunities to apply these preparations as antioxidants.

AroniaPlants: A Review of Traditional Use, Biological Activities, and Perspectives for Modern Medicine

The Aronia genus (Rosaceae family, Maloideae subfamily) includes two species of native North American shrubs: Aronia melanocarpa (Michx.) Ell. (black chokeberry) and Aronia arbutifolia (L.) Pers. (red chokeberry). The fruits of A. melanocarpa have been traditionally used by Potawatomi Native Americans to cure colds. In the first half of the 20(th) century, cultivars of black chokeberry were introduced to the Soviet Union and other European countries, providing fruits used by food industry. At present, it is used mainly for juice, jam, and wine production, as well as an ornamental plant. Among other substances, the berries of A. melanocarpa contain anthocyanins and procyanidins, possessing strong antioxidative potential. Numerous health-promoting activities-namely, antioxidative, antimutagenic, anticancer, cardioprotective, hepatoprotective, gastroprotective, antidiabetic, anti-inflammatory, antibacterial, antiviral, radioprotective, and immunomodulatory-have been demonstrated for black chokeberry extracts by both in vitro and in in vivo studies. The presented review summarizes the information concerning botany, cultivation, chemical composition, and pharmacological activities of Aronia plants.

Chokeberry extract consumption inhibits weight gain by modulating adipogenesis, insulin signaling, and inflammatory related gene expression in adipose tissue in rats fed a fructose rich diet

Chokeberries are a rich source of anthocyanins which may contribute to the prevention of weight gain and obesity. The aim of present study was to determine if an extract from chokeberries inhibits weight gain in rats fed a fructose‐rich diet (FRD, 60%) and explore the potential molecular mechanisms related to adipogenesis, insulin signaling, and inflammatory related pathways in epididymal adipose tissue (EAT). Chokeberry extract (CB, CellBerry®, 200 mg/kg daily) was added to the drinking water for 6 wks in rats made insulin resistant by feeding a FRD. Chronic CB intake lowered body weight gain, epididymal fat accumulation, blood glucose, triglycerides, cholesterol, and LDL‐C in the FRD‐induced insulin resistant rats and improved glucose intolerance and elevated plasma adiponectin levels. Gene expression of adiponectin, PPARg, IRS1, IRS2, PI3K, and glycogen synthesis 1 were all improved by the CB supplement. The levels of adipocyte gene expression of inflammatory genes such as IL‐1b, IL‐6 and TNF‐α were lowered by CB. In summary, these results suggest that the chokeberry extract (CellBerry®) inhibited weight gain in FRD‐induced insulin resistant animals, and decreased risk factors related to insulin resistance by modulating multiple genes associated with adipogenesis, insulin signaling, and inflammation. (Funded by USDA/ARS CRADA No.58‐3K95‐7‐1184 with Integrity Nutraceuticals International).

Experimental in vitro arterial reactivity and tissue culture solutions alter the time-dependent stability of anthocyanins from elderberry, chokeberry, and bilberry extracts

We examined the effect of solutions commonly used for in vitro assessment of blood vessel physiology and pharmacology on the half-lives of monomeric anthocyanins contained in extracts from elderberry, chokeberry, and bilberry. We observed that monomeric anthocyanin degradation in all extracts was accelerated when they were solubilized in an in vitro vascular physiological salt solution (PSS) compared with extracts in purified water. Degradation was accelerated further by increasing the temperature of the PSS to 37°C and bubbling it with 95% oxygen/5% carbon dioxide. A common, complex, tissue culture media yielded similar results to the physiological salt solution at 37°C. We also observed that the percentage polymeric color estimated by bisulfite bleaching corresponded to monomeric degradation in PSS. These results suggest that exposure of anthocyanins to physiological conditions that mimic those in the human body may stimulate the conversion of monomeric anthocyanins to their polymeric forms. Such conversion would probably contribute to the effects of anthocyanins on physiological functions in in vitro experiments and needs to be considered when evaluating effects of these compounds on physiological processes.

Anti-neurodegenerative activity of photosensitizing dyes (3): The effect on a hereditary cerebellar ataxia

Chokeberries (Aronia melanocarpa (Michx.) Elliot have recently become one of the most popular and widely used berry fruits, and there are numerous studies dealing with the investigation of their chemical composition and biological activities. Unlike berries, chokeberry leaves were far less investigated. Therefore, the aim of this study was to conduct a bioactivity-based analysis of chokeberry leaves collected after berries were harvested. Chemical analysis of hydroethanolic chokeberry extract and its ethyl acetate, n-butanol, and water fractions was performed. Antioxidant, hypoglycemic, and antineurodegenerative activities of the obtained samples were assessed by in vitro tests. The highest total phenolics content was found in n-butanol fraction (221.5 mg gallic acid equivalents/g dw). Fourteen compounds (six phenolic acids and eight flavonoids) were identified in the samples. Caffeoylquinic acid derivatives and quercetin glycosides were dominant phenolic compounds. The highest content of phenolic acids, as well as flavonoids, was recorded in n-butanol fraction (80.75 mg/g dw and 47.79 mg/g dw, respectively). This fraction was the most active in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Also, the n-butanol fraction was the most effective inhibitor of acetylcholinesterase (AChE) and tyrosinase (TYR) enzymes. All samples showed a better inhibitory effect on α-glucosidase enzyme with inhibition concentrations IC50 = 4.21 - 9.22 μg/mL, than α-amylase enzymes (IC50 = 14.36 - 88.61 μg/mL). Pearson’s correlation between the content of individual phenolics and the results of biological tests was performed. Thus, hyperoside and isoquercitrin showed a significant correlation with DPPH and ABTS tests, caffeoylquinic acids with FRAP test, quercetin 3-O-vicianoside with β-carotene assay, hyperoside and isoquercitrin with α-amylase inhibition activity, and isorhamnetin 3-O-rutinoside with α-glucosidase inhibition assay. Considering the obtained results, chokeberry leaves represent a valuable natural source of phenolic compounds with promising potential for the development of new products with beneficial effects on human health.

Physiological influence of chokeberry phenolics in model diet

Seven groups of Wistar rats (8 males in each) were fed for 4 weeks diets with chokeberry products. Chokeberry juice was added every day to diets at a dose of 1.5, 3 and 6 ml per rat (corresponding to the intake of about 0.5, 1 and 2 l of juice by an adult person) or diets were supplemented with polyphenolics extract to reach the same level of phenolics. The addition of juice or extract did not affect food intake and body gain. Chokeberry juice increased stomach pH from 3.44 (control group) to 3.69–3.85, and ileal pH from 6.16 to 6.23–6.46. Alkalisation of digesta was less distinct with diets containing polyphenolics extract. Both chokeberry products decreased the concentration of caecal ammonia, especially at medium and high doses. The highest dose of chokeberry juice increased microbial α-glucosidase, decreased β-glucosidase and had no effect on β-glucuronidase activities in the caecal digesta. To compare with the control group, the highest dose of chokeberry juice and extract numerically decreased triglycerides (from 265 to 211 and 219 mg dl –1 , respectively) and significantly decreased total cholesterol level in the serum (from 133 to 118 and 114 mg dl –1 , respectively) and increased content of butyrate in short-chain fatty acids sum of caecal digesta. Indices of the antioxidant status of rats were similar in all treatments. Physiological results of applying relatively low amount of phenolic extract in the diet were similar as when applying high doses of chokeberry juice.

Low concentration of anthocyanin enriched extracts from chokeberry attenuate lipid oxidation of isolated porcine coronary arteries in vitro.

We have reported previously that impaired endothelium‐dependent, NO mediated relaxation of porcine coronary arteries, resulting from either external or internal superoxide exposure, is prevented by simultaneous exposure of the arteries to chokeberry extract ( 0.05mg total anthocyanin/L). We examined whether this concentration of extract could attenuate generalized oxidation of arterial lipids in vitro. Female porcine coronary artery rings were incubated for 1–2 days in plates of sterile tissue culture media in an O2/CO2 incubator at 37Co. Exposure of rings to exogenous superoxide by pyrogallol or endogenous superoxide by inhibition of Mg/Cu SOD, at levels shown to impair NO mediated coronary relaxation, did not result in detectable accumulation of oxidized tissue lipids as assessed by TBARS formation. Following 2 days incubation of rings in tissue culture media, oxidant stress of rings from a 2hr exposure to 250uM FeSO4+15uM ascorbic acid, shown previously to produce 40% cell toxicity, produced significant formation of arterial TBARS (0.133±0.022 vs. 0.075±0.006, mean/SEM, nmol TBARS/mg prot., n = 4, p<0.05). However, TBARS formation was reduced by 27% in rings exposed to chokeberry (0.05 mgTa/L) for 4 hrs on day 1 of incubation followed by 6 hrs on day 2. We conclude that low concentration of anthocyanin enriched chokeberry extracts, previously shown to protect arterial relaxation from oxidant impairment, also protects coronary arteries from generalized oxidation of membrane lipids. Our results suggest that such extracts may provide protection of coronary arteries from oxidant injury commonly associated with cardiovascular disease.

Anthocyanins Exist in the Circulation Primarily as Metabolites in Adult Men

Anthocyanins are reported to have many "health promoting" properties; however, despite numerous reports of their bioactivities, their absorption and metabolism in humans are poorly understood. The objective of this research was to detail the pharmacokinetic parameters of anthocyanins after the administration of a 721-mg oral dose of cyanidin 3-glycosides from chokeberry extract to human subjects. Solid-phase extraction, preparative-HPLC, preparative-TLC, HPLC-diode array detection, HPLC-MS, and NMR were utilized to isolate, identity, and quantify anthocyanins in 0- to 7-h (0, 1, 2, 3, 4, 5, 6, 7 h) serum and 0- to 24-h urine samples (total individual urine voids over 24 h). The cumulative concentration of total anthocyanins (parent and metabolites) detected in the serum (0-7 h) was 376.65 +/- 16.20 (nmol x h)/L (area under the concentration time curve), reaching a maximum concentration (C(max) = 96.08 +/- 6.04 nmol/L) within 2.8 h. The parent anthocyanins represented only 32.0% [120.63 +/- 2.85 (nmol x h)/L] of the total anthocyanins detected with 68.0% [256.02 +/- 5.23 (nmol x h) identified as conjugated metabolites. Additionally, the total urinary excretion of anthocyanins over 24 h was 1071.54 +/- 375.46 microg, reaching a maximal rate of excretion (R(max) = 202.74 +/- 85.06 microg/h) at 3.72 +/- 0.83 h. Parallel to the serum data, only 32.5% (347.85 +/- 60.61 microg) of the anthocyanins excreted in the urine (total 24 h) were the parent compounds with 67.5% (723.69 +/- 92.59 microg) occurring as conjugated metabolites. The metabolites were identified as glucuronidated and methylated derivatives of the parent cyanidin 3-glycosides. The above results indicate that cyanidin 3-glycosides are rapidly absorbed and metabolized extensively following a moderate-to-high oral dose in humans.

Anthocyanin metabolites in human urine and serum.

In the present study we investigated the metabolic conversion of cyanidin glycosides in human subjects using solid-phase extraction,HPLC-diode array detector, MS, GC, and enzymic techniques. Volunteers consumed approximately 20 g chokeberry extract containing 1.3 g cyanidin 3-glycosides (899 mg cyanidin 3-galactoside, 321 mg cyanidin 3-arabinoside, 51 mg cyanidin 3-xyloside and 50 mg cyanidin 3-glucoside). Blood samples were drawn at 0, 0.5, 1, and 2 h post-consumption of the extract. Urine samples were also collected at 0, 4-5,and 22-24h. We have confirmed that human subjects have the capacity to metabolise cyanidin 3-glycosides, as we observed at least ten individual anthocyanin metabolites in the urine and serum. Average concentrations of anthocyanins and anthocyanin metabolites in the urine reached levels of 17.9 (range 14.9-20.9) l.mol/l within 5 h post-consumption and persisted in 24h urine samples at levels of 12.1 (range 11.1-13.0) nmol/l. In addition, average total levels of anthocyanins and anthocyanin metabolites detected in the serum were observed at 5917 (range 197.3-986.1) nmol/ within 2h post-consumption. Cyanidin 3-galactoside accounted for 55.4% (9.9(range 7-2-12-6) l.mol/) and 66.0% (390.6 (range 119.4-661-9) nmol V) of the detected anthocyanins in the urine and serum samples,respectively. The metabolites were identified as glucuronide conjugates, as well as methylated and oxidised derivatives of cyanidin 3-galactoside and cyanidin glucuronide. Conjugation probably affects the biological activity of anthocyanins and these metabolic products are likely in part responsible for the reported health benefits associated with the consumption of anthocyanins.

Second and Third Derivatives of UV Spectra as a Tool for Identification of Major Anthocyanins from Aronia melanocarpa Extract, Separated Using Reversed-Phase High-Performance Liquid Chromatography

The aim of the study was to propose a method for identification of major anthocyanins in black chokeberry: cyanidin 3-O-β-D-galactopyranoside and cyanidin 3-O-α-L-arabinopyranoside, using reversed-phase high-performance liquid chromatography on line with UV spectroscopy. The similarity indexes between standard spectra and spectra of major components of black chokeberry extract were calculated. The calculations were performed for zero-order spectra and first-fifth derivatives. Only the second and third derivatives of UV spectra provided correct identification of the compounds investigated. Third derivatives of spectra gave higher values of the parameters (calculated using Student's test) indicating statistical significance between similarity indexes to the derivatives of spectra of anthocyanin standards. Third derivative UV spectroscopy may be thus recommended as a tool to identify anthocyanins.

2P-0473 Effect of anthocyanins from chokeberry (Aronia melanocarpa) on blood pressure, inflammatory mediators and cell adhesion molecules in patients with a history of myocardial infarction (MI)

Endothelial progenitor cells (EPC) may provide protection against atherosclerosis and plaque rupture by their innate ability to replace dysfunctional or damaged endothelial cells in plaque microvessels. There is evidence that angiotensin II may impair the angiogenic functions of EPCs in the atherosclerotic plaque by accelerating senescence and inhibiting their proliferation through oxidative stress induction.In this study, we examined whether chokeberry (Aronia melanocarpa) fruit extract, containing mainly anthocyanins with potent antioxidative properties, could protect EPCs against angiotensin-induced oxidative stress.EPCs were isolated from peripheral blood of young healthy volunteers and cultivated on fibronectin-coated plates in the presence or absence of angiotensin II (1 µM) and chokeberry extract (1–25 µg/ml).EPCs exposed to chokeberry extract prior to angiotensin II showed a significant increase of proliferation and telomerase activity, and a decrease in the percentage of senescent cells and intracellular ROS formation in comparison to angiotensin II treated cells. Furthermore, extract increased migration ability, adhesion to fibronectin and the angiogenic potential of EPC in vitro diminished by angiotensin II in a concentration-dependent manner. That effect was related to the activation of the Nrf2 transcription factor and the increase of HO-1 expression.Our results suggested that chokeberry extract may protect EPCs against angiotensin II-induced dysfunction and could play a potential role in the prevention of coronary artery disease.

The potential for strategies using micronutrients and heterocyclic drugs to treat invasive gliomas.

Local invasion of neoplastic cells into the surrounding brain is perhaps the most important aspect of the biology of gliomas that precludes successful therapy. Despite significant advances in neuro-imaging, neurosurgery and radiotherapy, the median survival for patients with a malignant glioma is still less than one year. With the increasing knowledge of the biology of brain tumours, derived from cellular and molecular studies, new methods of treatment are being developed with some success. Approaches studied already include anti-invasive, pro-apoptotic and anti-angiogenesis strategies and clinical trials are imminent. In this article we review two new approaches to the management of gliomas: nutraceutical intervention and heterocyclic drugs. The first approach uses a combination of naturally occurring agents, including citrus flavonoids, chokeberry extract, red grape seed extract, lycopene, selenium and red clover extract. These agents can either trigger apoptosis or affect the pathways underlying diffuse invasion. The second approach involves the use of a heterocyclic drug, clomipramine, which selectively triggers apoptosis in neoplastic cells but not in normal glia. The article refers to the results of recent studies performed in our laboratory which suggest that these new approaches can be translated into benefit to patients.