RESUMO
BACKGROUND: This study assessed the influence of the haptoglobin phenotype on markers regulating inflammation in patients with type 2 diabetes. METHODS: The haptoglobin phenotypes, soluble form of CD163 receptor (sCD163), p53 concentrations and high mobility group box protein 1 (HMGB1), interleukin 10 (IL-10) secretion in serum were assayed via ELISA tests. In the first part of the project, patients were divided into three groups which differed by the haptoglobin phenotype, and afterwards into two groups according to the criterion of the presence or absence of cardiovascular disease. RESULTS: Diabetic patients with haptoglobin phenotype 1-1 (Hp1-1) had a significantly higher concentration of IL-10 and sCD163 compared to haptoglobin phenotype 2-1 (Hp2-1) and haptoglobin phenotype 2-2 (Hp2-2). Moreover, diabetic patients with Hp1-1 had a significantly lower concentration of p53 and HMGB1 compared to diabetic patients with Hp2-1 and Hp2-2. The results have shown that diabetics with Hp2-1 had a significantly lower postprandial glucose level compared to diabetics with Hp2-2. Apart from that, there were no differences in the occurrence of haptoglobin variants between patients with or without cardiovascular disease. CONCLUSIONS: Our study provides new data for a relationship between the type of haptoglobin in patients with type 2 diabetes and the concentration of factors that regulate the body's inflammation. We have shown that the Hp1-1 can serve as a genetic marker of inflammatory processes.
Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Complicações do Diabetes/genética , Diabetes Mellitus Tipo 2/genética , Proteína HMGB1/sangue , Haptoglobinas/genética , Interleucina-10/sangue , Receptores de Superfície Celular/sangue , Proteína Supressora de Tumor p53/sangue , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Marcadores Genéticos/genética , Humanos , Inflamação/sangue , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Fatores de RiscoRESUMO
BACKGROUND: Oleacein is a secoiridoid group polyphenol found mostly in Olea europea L. and Ligustrum vulgare L. (Oleaceae). The aim of the present study was to investigate a potential role of oleacein in prevention of the foam cell formation. MATERIALS AND METHODS: Oleacein was isolated from Ligustrum vulgare leaves. Human monocyte-derived macrophages were obtained from monocytes cultured with Granulocyte-macrophage colony-stimulating factor (GM-CSF)Then, cells were incubated with 20 M or 50 M of oleacein and with oxidized low-density lipoprotein (oxLDL) (50 g/mL). Visualization of lipid deposition within macrophages was carried out using Oil-Red-O. Expression of CD36, Scavenger receptor A1 (SRA1) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) was determined by Reverse transcription polymerase chain reaction (RT-PCR) and by flow cytometry. Apoptosis was determined by flow cytometry using Annexin V assay. STAT3 and Acyl-coenzyme A:cholesterol acyltransferase type 1 (ACAT1)levels were determined by ELISA. P-STAT3, P-JAK1, P-JAK2 expressions were determined by Western blot (WB). RESULTS: Oleacein in dose-dependent manner significantly reduced lipid deposits in macrophages as well as their expression of selected scavenger receptors. The highest decrease of expression was found for CD36 and SRA1 receptors, from above 20% to more than 75% compared to oxLDL and the lowest for LOX-1 receptor, from approx. 8% to approx. 25% compared to oxLDL-stimulated macrophages. Oleacein significantly reduced (2.5-fold) early apoptosis of oxLDL-stimulated macrophages. Moreover, oleacein significantly increased the protein expression of JAK/STAT3 pathway and had no effect on ACAT1 level. CONCLUSIONS: Our study demonstrates, for the first time, that oleacein inhibits foam cell formation in human monocyte-derived macrophages and thus can be a valuable tool in the prevention of early and advanced atherosclerotic lesions.
RESUMO
BACKGROUND AND PURPOSE: Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production, and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. EXPERIMENTAL APPROACH: PGG was administered to mice every 2 days at a dose of 10 mg·kg-1 i.p during 14 days of Ang II infusion. It was used at a final concentration of 20 µM for in vitro studies in cultured cells. KEY RESULTS: Ang II administration increased leukocyte and T-cell content in perivascular adipose tissue (pVAT), and administration of PGG significantly decreased total leukocyte and T-cell infiltration in pVAT. This effect was observed in relation to all T-cell subsets. PGG also decreased the content of T-cells bearing CD25, CCR5, and CD44 receptors and the expression of both monocyte chemoattractant protein 1 (CCL2) in aorta and RANTES (CCL5) in pVAT. PGG administration decreased the content of TNF+ and IFN-γ+ CD8 T-cells and IL-17A+ CD4+ and CD3+ CD4- CD8- cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II-infused animals independently of the BP increase. Mechanistically, PGG (20 µM) directly inhibited CD25 and CCR5 expression in cultured T-cells. It also decreased the content of IFN-γ+ CD8+ and CD3+ CD4- CD8- cells and IL-17A+ CD3+ CD4- CD8- cells. CONCLUSION AND IMPLICATION: PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.
Assuntos
Taninos Hidrolisáveis/farmacologia , Hipertensão/tratamento farmacológico , Inflamação/tratamento farmacológico , Disfunção Ventricular/tratamento farmacológico , Angiotensina II/administração & dosagem , Animais , Humanos , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/isolamento & purificação , Hipertensão/induzido quimicamente , Inflamação/metabolismo , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oenothera/química , Células Tumorais Cultivadas , Disfunção Ventricular/metabolismoRESUMO
BACKGROUND: Chronic hyperalgesia and allodynia associated with progressive damage of peripheral neurons are the most prevalent complications of diabetes mellitus. Plants belonging to the family of Oleaceae were traditionally used in folk medicine for the management of diabetes. HYPOTHESIS/PURPOSE: The aim of this study was to investigate whether an aqueous extract from the leaves of Ligustrum vulgare (common privet) could be useful to target neuropathic pain in a rat streptozotocin (STZ) model of diabetes. METHODS: The chemical composition of the aqueous extract from privet leaf was characterized with the UHPLC-DAD-MS method and the analytical quantification of its constituents was performed with HPLC-DAD. Mechanical hyperalgesia and allodynia were evaluated with the Randall-Selitto and von Frey tests. RESULTS: Our investigation revealed the presence of secoiridoids: oleacein (23.48⯱â¯0.87â¯mg/g), oleocanthal (8.44⯱â¯0.08â¯mg/g), oleuropein (1.50⯱â¯0.01â¯mg/g), as well as phenylpropanoids: echinacoside (6.46⯱â¯0.07â¯mg/g), verbascoside (4.03 ± 0.04â¯mg/g) and p-coumaroyl glucarates in the dried aqueous extract of privet leaves. Behavioral data indicated that chronic intraperitoneal administration of the extract (50-200â¯mg/kg) for 21 days resulted in a decrease in diabetes-induced hyperalgesia and allodynia. Blood glucose levels remained unaltered, while body weight and water intake decreased significantly. CONCLUSION: The aqueous privet leaf extract could serve useful in facilitating treatment of painful diabetic neuropathy. Additionally, the study showed that the antihyperalgesic activity of Ligustrum vulgare leaf extract is not likely related to its antihyperglycemic properties.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Ligustrum/química , Extratos Vegetais/farmacologia , Aldeídos , Animais , Cromatografia Líquida de Alta Pressão , Monoterpenos Ciclopentânicos , Glucosídeos , Glicosídeos , Hiperalgesia/tratamento farmacológico , Glucosídeos Iridoides , Iridoides/uso terapêutico , Masculino , Neuralgia/tratamento farmacológico , Fenóis , Folhas de Planta/química , Ratos , EstreptozocinaRESUMO
BACKGROUND: In patients with hypertension the haemorrhage into carotid atherosclerotic plaque increases risk of plaque destabilization and rupture. Our previous study showed that oleacein, a secoiridoid present in extra virgin olive oil, enhanced uptake of haemoglobin-haptoglobin complex and change macrophage phenotype from pro-inflammatory M1 to anti-inflammatory M2. PURPOSE: The aim this study was to investigate a potential role of oleacein in attenuation of carotid plaque destabilisation ex vivo. METHODS: Samples of atherosclerotic plaque were harvested from 20 patients with hypertension /11 women and 9 men/, who underwent carotid endarterectomy after transient ischemic attacks. Matching pieces of each plaque were incubated with increased concentration of pure oleacein /range 0-20 µM/ for 24 h. HMGB1, MMP-9, MMP-9/NGAL, TF and IL-10, as well as HO-1 secretion from plaque was measured by enzyme-linked immunosorbent assay /ELISA/. Statistical significance was set at P < 0.05 and P < 0.001. RESULTS: Oleacein at the concentrations of 10 and 20 µM significantly (P < 0.001) decreased secretion of HMGB1 (up 90%), MMP-9 (up to 80%), MMP-9/NGAL complex (up to 80%) and TF (more than 90%) from the treated plaque, as compared to control. At the same time IL-10 and HO-1 release increased by more than 80% (P < 0.001). CONCLUSION: Our results indicate that oleacein possess ability to attenuate the destabilization of carotid plaque and could be potentially useful in the reduction of ischemic stroke risk.
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Aldeídos/farmacologia , Proteína HMGB1/metabolismo , Fenóis/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Idoso , Endarterectomia das Carótidas , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-10/metabolismo , Ataque Isquêmico Transitório/cirurgia , Lipocalina-2/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden deaths due to overdosing, attempts have been made to introduce co-analgesics. Due to an increasing amount of data concerning a potential enhance of opioid analgesia by the physiological antagonist of N-methyl-d-aspartate receptors, magnesium ions (Mg2+), a concomitant use of such a combination seems to be interesting from a clinical point of view. Therefore, the aim of this review is to provide an analysis of existing preclinical and clinical studies in the context of the benefits of using this combination in clinical practice. A potential mechanism of magnesium - opioid interaction is also suggested. The potential influence of Mg on opioid adverse/side effects as well as conclusions on the safety of combined administration of magnesium and opioid drugs were also summarized. Data from animal studies indicate that magnesium increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well as acute pain. In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids. However, more clinical studies are needed concerning an influence of Mg on opioid activity in other difficult to treat types of pain, especially neuropathic and inflammatory.
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Analgésicos Opioides/farmacologia , Analgésicos/farmacologia , Magnésio/farmacologia , Neuralgia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Analgesia/métodos , Animais , Tolerância a Medicamentos , Humanos , Medição da Dor/métodos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
PURPOSE: As previously reported, magnesium sulphate administered parenterally significantly increased an opioid antinociception in different kinds of pain. Since the typical form of magnesium salts are poorly and slowly absorbed from the gastrointestinal tract we examined whether their micronized form could increase opioids induced antinociception. METHODS: In behavioural studies on rats morphine, tramadol and oxycodone together with magnesium (lactate dihydrate, hydroaspartate, chloride) in micronized (particles of size D90 < 50 µm) and conventional forms were used. Changes in pain thresholds were determined using mechanical stimuli. The intestinal absorption of two forms of magnesium lactate dihydrate (at the doses of 7.5 or 15 mg ions) in the porcine gut sac model were also compared. RESULTS: Micronized form of magnesium lactate dihydrate or hydroaspartate but not chloride (15 mg of magnesium ions kg-1) enhanced the analgesic activity of orally administered opioids, significantly faster and more effective in comparison to the conventional form of magnesium salts (about 40% for oxycodone administered together with a micronized form of magnesium hydroaspartate). Moreover, in vitro studies of transport across porcine intestines of magnesium ions showed that magnesium salts administered in micronized form were absorbed from the intestines to a greater extent than the normal form of magnesium salts. CONCLUSIONS: The co-administration of micronized magnesium organic salts with opioids increased their synergetic analgesic effect. This may suggest an innovative approach to the treatment of pain in clinical practice.
Assuntos
Analgésicos Opioides/farmacologia , Compostos de Magnésio/farmacologia , Analgesia/métodos , Analgésicos/farmacologia , Animais , Sinergismo Farmacológico , Masculino , Morfina/farmacologia , Oxicodona/farmacologia , Medição da Dor/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Tramadol/farmacologiaRESUMO
INTRODUCTION AND OBJECTIVE: Dyslipidemia is the most common factor leading to ischemic heart disease, which is one of the leading causes of death. The use of statins is the most important preventative measure of ischemic heart disease; however, their efficacy in patients in Poland is still too low. The purpose of this study was to evaluate regional differences in achieving treatment goals in total cholesterol (TC) and LDL cholesterol levels in patients treated with statins on an outpatient basis. MATERIALS AND METHODS: A survey was used to evaluate efficacy of treatment, completed by 49,950 patients in Poland treated with statins in 2008. The territory of Poland was divided into 4 research regions: the Northeast (NE), Northwest (NW), Southeast (SE), and Southwest (SW) regions. RESULTS: The largest group of patients resided in the SW region, the smallest in the SE region. Participants of the study suffered from hypercholesterolemia, on average, for at least a year before completing the study survey. Effective treatment leading to achievement of target TC was observed in less than 10% of the patients. Rate of achievement of target cholesterol levels was highest in the NE region, lowest in the NW region. Cardiologists were more successful in achieving therapeutic goals than GPs. Similar correlations between regions and doctors' specializations were observed for LDL values. CONCLUSIONS: Significant differences in the efficacy of treatment with statins were observed among the study group and were evaluated based on achievement of target TC and LDL cholesterol levels. Better results achieved in the NE region may be because the region includes the Masovian province, which is the most economically developed region in Poland.
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Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lipoproteínas LDL/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipercolesterolemia/etiologia , Masculino , Pessoa de Meia-Idade , PolôniaRESUMO
The role of polyphenols in the cardiovascular diseases prevention is still a matter of scientific discussion. However, recent clinical studies indicate that intake of anthocyanins and in a lesser extent procyanidins can participate in prevention of hypertension and type 2 diabetes. Fruits of Aronia melanocarpa (chokeberry) are known to be a reach source of these polyphenols. Moreover, its extracts were shown to express strong antioxidant, antiinflammatory, vasorelaxant and antithrombotic properties. The aim of the review is to summarize the results of the hitherto research regarding the biological effects at the molecular and clinical level.
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Antocianinas/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Photinia , Fitoterapia , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Humanos , Hipertensão/prevenção & controleRESUMO
BACKGROUND: 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. PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
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Angiotensina II/farmacologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Photinia/química , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Citoproteção , Frutas/química , Heme Oxigenase-1/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Oleacein (dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol; 3,4-DHPEA-EDA) have been proven to possess antioxidant and anti-inflammatory activity. PURPOSE: In this study, we examined whether oleacein could increase CD163 and IL-10 receptor expression as well as HO-1 intracellular secretion in human macrophages. METHODS: Effect of oleacein (10 and 20 µmol/l) or oleacein together with complexes of haemoglobin (Hb) and haptoglobin 1-1 (Hp11) or haptoglobin 2-2 (Hp22) on expression of IL-10 and CD163 receptor was determined by Flow Cytometry. Expression of CD163mRNA was measured by real-time quantitative RT-PCR. Heme oxygenase 1 (HO-1) intracellular secretion in macrophages was investigated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Oleacein (OC) together with complexes HbHp11 or HbHp22 stimulated the expression of CD163 (30-100-fold), IL-10 (170-300-fold) and HO-1 secretion (60-130-fold) after 5 days of coincubation. The 2-fold (24 h), 4-fold (48 h) increase of CD163 mRNA level and its final (72 h) decrease was also observed. CONCLUSION: Our results suggested that oleacein enhances anti-inflammatory activity of complexes haemoglobin with haptoglobin 1-1 and 2-2 and could play a potential role in the prevention of inflammatory disease related to atherosclerosis.
Assuntos
Aldeídos/farmacologia , Anti-Inflamatórios/farmacologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Macrófagos/efeitos dos fármacos , Fenóis/farmacologia , Receptores de Superfície Celular/metabolismo , Antioxidantes/farmacologia , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Haptoglobinas/farmacologia , Heme Oxigenase-1/metabolismo , Hemoglobinas/farmacologia , Humanos , Macrófagos/metabolismo , Piranos , Receptores de Interleucina-10/metabolismoRESUMO
BACKGROUND: The human body requires folic acid (FA) to produce blood cells, secure cell division, and growth. Moreover, this vitamin is important in the prevention of cardiovascular disease (CVD). Because the results of studies on the use of FA in the prevention of CVD are ambiguous, it seems necessary to conduct further research, which will explain in which cases supplementation is effective. AIM: To assess the impact of FA supplementation on the coagulation, inflammatory, lipid parameters, and kidney function in subjects with atherosclerosis risk factors, depending on the content of FA in their diet. METHODS: The study enrolled 97 young adult Caucasian individuals (34 males and 63 females) with atherosclerosis risk factors. This population was divided into two groups: A--with low content of FA in the diet (< 40% of reference daily intake) and B--with moderate content of FA in the diet (40-90% of reference daily intake). The participants were asked to take FA in the low-dose of 0.4 mg/24 h for 3 months. RESULTS: Low-dose FA supplementation resulted in elevation of FA concentrations (79% vs. 75.1%) in the studied groups and, concomitantly, a decrease in homocysteine concentrations (21% vs. 20.3%). Mean level of creatinine decreased after FA supplementation in both groups (0.93 ± 1.1 vs. 0.72 ± 0.15 mg/dL and 0.83 ± 0.16 vs. 0.77 ± 0.15 mg/dL). These differences were statistically significant (p < 0.0001). The difference in mean estimated glomerular filtration rate values before and after FA supplementation was statistically significant in group A (p = 0.002) and on the border of statistical significance in group B (p = 0.06). CONCLUSIONS: FA supplementation has no influence on the coagulation, inflammatory and lipid parameters in subjects with atherosclerosis risk factors depending on the content of FA in their diet. However FA supplementation may have a beneficial effect on kidney function in subjects with low content of FA in the diet.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Ácido Fólico/farmacologia , Inflamação , Rim/fisiologia , Adulto , Aterosclerose/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Fatores de Risco , Adulto JovemRESUMO
Epidemiological studies suggest that the cardioprotective properties of olive oil, particularly extra-virgin type, result from a positive influence of its components, such as phenolic compounds, on the cardiovascular system. One of the most abundant phenolic compounds of extra virgin olive oil is the dialdehydic form of elenolic acid conjugated with 3, 4-(dihydroxyphenyl)ethanol (3, 4- DHPEA-EDA), also known as oleacein. Due to its abundance in olive oil, it may play a special role in decreasing the progression of atherosclerosis. Some bioactivities of oleacein, such as antioxidant, anti-inflammatory, anti-proliferative and antimicrobial, were documented. There is also evidence of the bioavailability of oleacein in humans as well. However, due to the lack of clinical data, further studies are needed to provide information about the usefulness of this compound in antiatherosclerotic therapy.
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Aldeídos/uso terapêutico , Aterosclerose/tratamento farmacológico , Dieta Mediterrânea , Fenóis/uso terapêutico , Aldeídos/farmacocinética , Aldeídos/farmacologia , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Disponibilidade Biológica , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Neutrófilos/efeitos dos fármacos , Fenóis/farmacocinética , Fenóis/farmacologiaRESUMO
Polyphenols, such as oleacein (3,4-DHPEA-EDA; 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde), are believed to play a role in the prevention of cardiovascular diseases. Due to an increase of neutrophil mediators in acute myocardial infarction the aim of this study was to establish the effect of oleacein on neutral endopeptidase (NEP) activity and other functions of human neutrophils, such as elastase, MMP-9 and IL-8 production. The effect on CD62L and CD11b/CD18 expression on neutrophils was also determined. Oleacein with a concentration of 100 µM inhibited NEP activity, elastase, MMP-9 and IL-8 release from neutrophils by 77.7 ± 2.7%, 21.3 ± 7.8%, 22.7 ± 4.2% and 25.2 ± 5.6%, respectively. Oleacein with a concentration of 50 µM suppressed CD11b/CD18 expression by 63.6 ± 3.1% and to a lesser extent, increased CD62L expression by 27.3 ± 8.3% on the surface of neutrophils, in comparison with stimulated cells. Oleacein by inhibiting NEP activity, adhesion molecules expression and elastase release might play a role in the protective effects of olive oil against endothelial injuries.
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Aldeídos/farmacologia , Antígeno CD11b/genética , Antígenos CD18/genética , Inibidores Enzimáticos/farmacologia , Neprilisina/antagonistas & inibidores , Neutrófilos/efeitos dos fármacos , Elastase Pancreática/metabolismo , Fenóis/farmacologia , Piranos/farmacologia , Antígeno CD11b/metabolismo , Antígenos CD18/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Neprilisina/genética , Neprilisina/metabolismo , Neutrófilos/enzimologia , Neutrófilos/metabolismo , Azeite de Oliva , Elastase Pancreática/genética , Extratos Vegetais/farmacologia , Óleos de Plantas/químicaAssuntos
Placa Aterosclerótica/prevenção & controle , Anti-Hipertensivos/uso terapêutico , Apolipoproteína B-100/antagonistas & inibidores , Plaquetas/fisiologia , Antagonistas dos Receptores CCR5 , Quimiocina CCL5/antagonistas & inibidores , HDL-Colesterol/efeitos dos fármacos , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/prevenção & controle , Citocinas/metabolismo , Diagnóstico por Imagem , Endotélio Vascular/fisiologia , Testes Genéticos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucócitos/patologia , Neovascularização Fisiológica/fisiologia , Niacina/uso terapêutico , Peptídeo Hidrolases/fisiologia , Fosfolipases/antagonistas & inibidores , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/patologia , Inibidores da Agregação Plaquetária/uso terapêutico , Pró-Proteína Convertase 9 , Pró-Proteína Convertases/antagonistas & inibidores , Receptores CCR5 , Serina Endopeptidases , Fumar/efeitos adversos , Células-Tronco/fisiologia , Estresse Fisiológico/fisiologiaRESUMO
UVA radiation stimulates the production of reactive oxygen species (ROS), which react with lipids, proteins and other intracellular molecules leading to oxidative stress, cellular damage and ultimately cell death. There is, therefore, a growing need for substances exhibiting antioxidant activity, which may support repair mechanisms of the skin. This study evaluates the protective effect of the aqueous Oenothera paradoxa Hudziok defatted seeds extract, rich in polyphenolic compounds, against UVA (25 and 50J/cm(2))-induced changes in normal human dermal fibroblasts (NHDFs). The tested extract (0.1-10µg/ml) has decreased, in a concentration-dependent fashion, the UVA-induced release of lactate dehydrogenase (LDH) into the culture medium, the ROS production (with the use of 2',7'-dichlorodihydrofluorescein diacetate) and lipid peroxidation (utilizing redox reactions with ferrous ions) as compared to the control cells (incubated without the extract). Moreover, the extract increased the number of viable (calcein positive) cells decreasing the number of cells in late apoptosis (annexin V-FITC and propidium iodide positive). Thus our results show that O. paradoxa defatted seeds extract may be beneficial for the prevention of UVA skin damage.
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Derme/citologia , Fibroblastos/citologia , Oenothera/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/química , Raios Ultravioleta/efeitos adversos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Necrose , Protetores contra Radiação/farmacologia , Água/químicaRESUMO
Endothelial progenitor cells (EPCs) are responsible for neovascularization of ischaemic tissue and may participate in re-endothelization of an injured arterial wall. There is evidence that angiotensin II, by an increase of gp91phox expression and induction of ROS generation, accelerates cell senescence and impairs functions of EPCs. Oleacein is a main phenolic compound from olive oil, whereas oleuropein is present in olive leaves. Both compounds possess antioxidative, hypotensive and anti-inflammatory properties and show beneficial activity on the cardiovascular system. In this study, we examined whether oleoeuropein and oleacein could protect EPCs against impairment of their functions due to angiotensin-induced cell senescence. CD31(+)/VEGFR-2(+) cells were isolated from young healthy volunteers blood samples and cultured on fibronectin-coated plates with angiotensin (1.0µM) in presence or absence of increasing concentrations (from 1.0 to 10.0 µM) of oleoeuropein or oleacein. As compared to angiotensin II-treated cells, EPCs exposed to oleacein or oleuropein 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. Oleacein and oleuropein restored migration, adhesion and tube formation of EPCs diminished by angiotensin II in a concentration-dependent manner. This effect was related to NF-E2-related factor 2 (Nrf2) transcription factor activation and the increase of heme oxygenase-1 (HO-1) expression.
Assuntos
Aldeídos/farmacologia , Angiotensina II/farmacologia , Heme Oxigenase-1/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fenóis/farmacologia , Piranos/farmacologia , Células-Tronco/efeitos dos fármacos , Adulto , Aldeídos/química , Adesão Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Voluntários Saudáveis , Heme Oxigenase-1/metabolismo , Humanos , Glucosídeos Iridoides , Iridoides , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fenóis/química , Piranos/química , Espécies Reativas de Oxigênio/metabolismo , Células-Tronco/metabolismoRESUMO
OBJECTIVES: The aim of this work was to determine the effect of standardized aqueous extracts from Epilobium angustifoliumâ L., E. parviflorumâ Schreb. and E. hirsutumâ L. herbs on the apoptosis of hormone-dependent prostate cancer cells (LNCaP). METHODS: The extracts were characterized using high-performance liquid chromatography-diode array detector coupled with mass spectrometry (HPLC-DAD-MS/MS). Apoptosis in the cells was analysed using Annexin V-fluorescein isothiocyanate, and mitochondrial potential, Δψm , using JC-1 by flow cytometry. Caspase-3 activity was determined by enzyme-linked immunosorbent assay. KEY FINDINGS: Using the HPLC-DAD-MS/MS method, 38 constituents were characterized. Extracts contained significant amounts of oenothein B as well as flavonoids and phenolic acids. Exposure of LNCaP cells to the extracts (20, 50 and 70 µg/ml) resulted in a significant increase in the level apoptotic cells, from 2.86 ± 0.5% (for untreated cells) up to 86.6 ± 1.0%. All extracts significantly decreased the mitochondrial potential, Δψm , resulting in an increase in the activity of caspase-3 from 0.3 ± 0.07 ng/mg of protein (for untreated cells) up to 1.26 ± 0.32 ng/mg of protein. CONCLUSIONS: This study demonstrated that Epilobium extracts are active against LNCaP prostate cancer cells and that their apoptotic activity is related to activation of the mitochondrial pathway. The high oenothein B content may influence the biological activity of these plant materials.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Epilobium/química , Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Neoplasias da Próstata/patologia , Espectrometria de Massas em TandemRESUMO
INTRODUCTION: Family history of stroke is an independent risk factor for cardiovascular disease (CVD). OBJECTIVES: The aim of this study was to evaluate selected metabolic risk factors and an association between the interaction of family history of premature ischemic stroke (PIS) and homocysteine (Hcy) levels with other risk factors in individuals with family histo ry of PIS. PATIENTS AND METHODS: The study involved 344 healthy individuals, including 143 with family history of PIS and 201 without family history of PIS (control group). RESULTS: In the group with family history of PIS, a significantly higher mean body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), ApoB/ apolipoprotein A-I (ApoA-I), and glucose values were observed in women, while in men, significantly higher mean values of BMI, SBP and DBP, total cholesterol (TC), LDL-C, ApoB/ApoA-I, and lower ApoA-I. There was a significant interaction of family history of PIS × Hcy for TC/high-density lipoprotein cholesterol (HDL-C), HDL-C, and triglycerides (TG) in women, and for TC/HDL-C, TC, and TG in men. Higher Hcy levels were associated with significantly higher values of TC/HDL-C and TG both in men and women, and with lower HDL -C levels in women and higher T C and LDL-C levels in men. CONCLUSIONS: Men and women with family history of PIS are characterized by an unfavorable shift in the risk factor profile. This effect is additionally enhanced by higher Hcy levels, which might be an indication for primary prevention in these individuals.
Assuntos
Homocisteína/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Adolescente , Adulto , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Biomarcadores/metabolismo , Glicemia/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Primária/métodos , Fatores de Risco , Caracteres Sexuais , Acidente Vascular Cerebral/prevenção & controle , Triglicerídeos/sangue , Adulto JovemRESUMO
BACKGROUND: According to epidemiological studies, dyslipidaemia is the commonest risk factor of atherosclerosis in the Polish population. It is estimated that 18 million adult Poles are affected by dyslipidaemia. AIM: The purpose of this study was to evaluate the quality of the statin therapy in high-risk Polish outpatients. METHODS: The 3ST-POL study involved 49,950 Polish outpatients. The enrolled patients met the following inclusion criteria: age between 40 and 85 years and a history of a minimum three months of statin therapy. A full lipid profile was screened in each patient; 72% of all subjects were high-risk patients. RESULTS: Among the patients in the 3ST-POL study, women represented 53%, and the mean age was 59.5 ± 10.8 years. Patients were treated by: general practitioners (GPs) 78.95%; diabetologists 5.02%; and cardiologists 16.03%. The most frequently used statins were atorvastatin and simvastatin. The most common dose was 20 mg/24 h. In the high-risk population, the lowest recommended total cholesterol (TC) concentration was achieved in 3.7% of treated subjects, whereas 5.6% of patients attained LDL < 80 mg/dL (2.0 mmol/L). 9.5% of patients did not exceed the upper limit of normal values for TC (155-175 mg/dL; 4.0-4.5 mmol/L) and 12.6% of patients reached LDL between 80-100 mg/dL (2.0-2.5 mmol/L). Subjects under the cardiologists' and diabetologists' care more often reached the recommended TC concentration (TC < 175 mg/dL; TC < 4.5 mmol/dL) and the difference was statistically important. CONCLUSIONS: This partial efficacy in dyslipidaemia control is not satisfactory.