Jana Muchová

Inhibition of NF-κB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol)

French maritime pine bark extract (Pycnogenol®) displays a variety of anti-inflammatory effects in vivo. Aim of this study was to determine whether human plasma after oral intake of Pycnogenol contains sufficient concentrations of active principles to inhibit key mediators of inflammation. Blood samples from seven healthy volunteers were obtained before and after five days administration of 200 mg Pycnogenol per day. Plasma samples statistically significantly inhibited matrix metalloproteinase 9 (MMP-9) release from human monocytes and NF-κB activation. Thus, we provide evidence that bioavailable active principles of Pycnogenol exert anti-inflammatory effects by inhibition of proinflammatory gene expression which is consistent with documented clinical observations. We suggest that our ex vivo method is suitable to substantiate molecular pharmacological mechanisms of complex plant extracts in a more focussed and rational way compared to in vitro studies by taking into account the processes of absorption and metabolism.

Influence of age on activities of antioxidant enzymes and lipid peroxidation products in erythrocytes and neutrophils of down syndrome patients

Thirty-seven individuals with Down syndrome (DS) were divided into four age categories: (i) 1 to < 6 years, (ii) 6 to < 13 years, (iii) 13 to < 20 years, and (iv) over 20 years. Activities of antioxidant enzymes found in individual age categories were different, but the differences between age groups were not statistically significant. We confirmed significantly higher activities of Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) in blood cells of people with DS as compared to 35 controls, which consisted, for the first time, of siblings of children with DS. No significant differences were found in activities of catalase and glutathione reductase in DS vs. controls. A significant difference was observed in serum concentration of malondialdehyde (MDA) in DS vs. controls (8.39 +/- 0.34 micromol/l vs. 7.34 +/- 0.27 micromol/l; p = .021) and concentration of MDA in erythrocytes of individuals with DS between the third and fourth age group (p = .05). In DS persons, an elevated ratio of SOD to catalase plus GPx with respect to the controls in all age categories was found, suggesting oxidative imbalance, potentially contributing to accelerated aging observed in these persons.

Antioxidant systems in polymorphonuclear leucocytes of Type 2 diabetes mellitus.

Aims To examine the effect of Type 2 diabetes mellitus (DM) on enzymes of importance for oxygen‐dependent killing of microorganisms by leucocytes.

Effect of polyphenolic extract, Pycnogenol®, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder

The purpose of this randomized, double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol® (Pyc) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine (8-oxoG) and on the total antioxidant status (TAS) in children with attention deficit/hyperactivity disorder (ADHD). We have found significantly increased damage to DNA in ADHD children when compared to controls. 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo group. TAS in ADHD children was lower in comparison to controls. After Pyc administration, TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application. Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children. In conclusion, Pycnogenol® administration reduces oxidative damage to DNA, normalizes TAS and improves attention of ADHD children. Explanation of mutual relation between oxidative damage to DNA, TAS and symptoms of ADHD and mechanism of Pycs action needs further investigations.

Single and multiple dose pharmacokinetics of maritime pine bark extract (Pycnogenol) after oral administration to healthy volunteers

BackgroundSince plant extracts are increasingly used as phytotherapeutics or dietary supplements information on bioavailability, bioefficacy and safety are warranted. We elucidated the plasma kinetics of genuine extract components and metabolites after single and multiple ingestion of the standardized maritime pine bark extract Pycnogenol (USP quality) by human volunteers.MethodsEleven volunteers received a single dose of 300 mg pine bark extract, five volunteers ingested 200 mg daily for five days to reach steady state concentrations. Plasma samples were obtained before and at defined time points after intake of the extract. Samples were analyzed by HPLC with ion-pair reagents and simultaneous UV and electrochemical detection.ResultsWe quantified total plasma concentrations of catechin, caffeic acid, ferulic acid, taxifolin and the metabolite M1 (δ-(3,4-dihydroxy-phenyl)-γ-valerolactone). Additionally, we describe plasma time courses and steady state appearance of ten so far unknown compounds, U1 to U10. After single ingestion, compounds derived from the extract were rapidly absorbed and the majority of them were detectable over whole experimental period of 14 h. The analysis of steady state plasma samples revealed significant phase II metabolism.ConclusionWe present the first systematic pharmacokinetic analysis of compounds derived from maritime pine bark extract. Beyond the known constituents and metabolites we uncovered the plasma time courses of ten unknown compounds. In concert with our previous detection of anti-inflammatory bioefficacy of these plasma samples ex vivo we suggest that constituents and metabolites of Pycnogenol bear potential for disclosure of novel active principles.

Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis.

Objective. The safe and efficacious use of Pycnogenol® (French maritime pine bark extract) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis (OA).

The effect of polyphenolic extract from pine bark, Pycnogenol® on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD)

Abstract Attention deficit hyperactivity disorder (ADHD) belongs to the neurodevelopmental disorders characterized by impulsivity, distractibility and hyperactivity. In the pathogenesis of ADHD genetic and non-genetic factors play an important role. It is assumed that one of non-genetic factors should be oxidative stress. Pycnogenol®, an extract from the pine bark, consists of bioflavonoids, catechins, procyanidins and phenolic acids. Pycnogenol® acts as powerful antioxidant, chelating agent; it stimulates the activities of some enzymes, like SOD, eNOS, and exhibits other biological activities. Aim: The aim of this randomized, double-blind, placebo-controlled trial was to investigate the influence of administered Pycnogenol® or placebo on the level of reduced (GSH) and oxidized (GSSG) glutathione in children suffering from ADHD and on total antioxidant status (TAS). This is the first investigation of the redox glutathione state in relation to ADHD. Results: One month of Pycnogenol® administration (1 mg/kg body weight/day) caused a significant decrease in GSSG and a highly significant increase in GSH levels as well as improvement of GSH/GSSG ratio in comparison to a group of patients taking a placebo. TAS in children with ADHD was decreased in comparison with reference values. Pycnogenol® administration normalizes TAS of ADHD children.

Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study.

BackgroundAssessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine.MethodsTwenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 μg), B6 (2.5 mg), folic acid (800 μg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16.ResultsThe serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma γ-tocopherol, β-carotene and retinol, except for reduction in α-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05).ConclusionsDaily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents.Trial registrationCurrent Controlled Trials ISRCTN89549017

Oxidative stress in women with perimenopausal symptoms.

Objective:In this study, we examined the relationships between perimenopausal symptoms, biochemical parameters, and markers of oxidative stress in women in perimenopause and compared them with those of premenopausal women. Methods:Sixty-two women (age, 53.2 ± 5.7 y) with perimenopausal symptoms were recruited to participate in our study. The control group consisted of 18 women without perimenopausal symptoms (age, 40 ± 5 y).Clinical perimenopausal symptoms were evaluated via the questionnaire of the Menopausal Rating Scale. Our participants were checked for basic biochemical parameters. The oxidative status of our samples was determined through the examination of lipoperoxides, 8-oxoguanine (8-oxoG) levels, and the total antioxidant status (TAS). Results:Perimenopausal women had higher total cholesterol values and lower paraoxonase-1 (PON1) activity compared to reference values. Other biochemical parameters as well as 8-oxoG levels were unchanged compared with those of healthy control women. Lipoperoxide levels were significantly increased compared with those of premenopausal women. We found an indirect correlation between PON1 arylesterase (PON1 A) activity and lipoperoxide levels, between PON1 A activity and atherogenic index, between age and TAS, and between age and 8-oxoG levels. DNA repair ability and the total antioxidant status of women in perimenopause were significantly increased compared with women in premenopause. Hypercholesterolemic women had significantly increased low-density lipoprotein cholesterol levels when compared with normocholesterolemic individuals, but these values were still within the reference range. Normocholesterolemic women had significantly decreased high-density lipoprotein cholesterol levels, below the reference range. We found no correlations between perimenopausal symptoms and biochemical parameters or oxidative stress markers. Conclusions:We found that women in perimenopause are under increased oxidative stress manifested by reduced PON1 A activity and elevated lipoperoxidation, DNA repair ability, and TAS. Nutritional antioxidant supplementation may be an effective approach in improving menopausal symptoms.

Probiotics and vitamin C for the prevention of respiratory tract infections in children attending preschool: a randomised controlled pilot study

Background:This pilot study investigates the efficacy of a probiotic consortium (Lab4) in combination with vitamin C on the prevention of respiratory tract infections in children attending preschool facilities.Subjects/methods:In a double-blind, randomised, placebo-controlled pilot study with children aged 3–6 years, 57 received 1.25 × 1010 colony-forming units of Lactobacillus acidophilus CUL21 (NCIMB 30156), Lactobacillus acidophilus CUL60 (NCIMB 30157), Bifidobacterium bifidum CUL20 (NCIMB 30153) and Bifidobacterium animalis subsp. lactis CUL34 (NCIMB 30172) plus 50 mg vitamin C or a placebo daily for 6 months.Results:Significant reductions in the incidence rate of upper respiratory tract infection (URTI; 33%, P=0.002), the number of days with URTI symptoms (mean difference: −21.0, 95% confidence interval (CI):−35.9, −6.0, P=0.006) and the incidence rate of absence from preschool (30%, P=0.007) were observed in the active group compared with the placebo. The number of days of use of antibiotics, painkillers, cough medicine or nasal sprays was lower in the active group and reached significance for use of cough medicine (mean difference: −6.6, 95% CI: −12.9, −0.3, P=0.040). No significant differences were observed in the incidence rate ratio or duration of lower respiratory tract infection or in the levels of plasma cytokines, salivary immunoglobulin A or urinary metabolites.Conclusions:Supplementation with a probiotic/vitamin C combination may be beneficial in the prevention and management of URTIs.