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1.
Int J Mol Sci ; 24(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37445909

RESUMO

Benign prostatic hypertrophy (BPH) is a noncancerous enlargement of the prostate gland that develops from hyper-proliferation of the stromal and epithelium region. Activation of pathways involving inflammation and oxidative stress can contribute to cell proliferation in BPH and tumorigenesis. Agricultural-waste-derived extracts have drawn the attention of researchers as they represent a valid and sustainable way to exploit waste production. Indeed, such extracts are rich in bioactive compounds and can provide health-promoting effects. In particular, extracts obtained from pomegranate wastes and by-products have been shown to exert antioxidant and anti-inflammatory effects. This study focused on the evaluation of the anti-angiogenic effects and chemopreventive action of a pomegranate extract (PWE) in cellular models of BPH. In our experimental conditions, we observed that PWE was able to significantly (p < 0.001) reduce the proliferation and migration rates (up to 60%), together with the clonogenic capacity of BPH-1 cells concomitantly with the reduction in inflammatory cytokines (e.g., IL-6, PGE2) and pro-angiogenic factor (VEGF-ADMA) release. Additionally, we demonstrated the ability of PWE in reducing angiogenesis in an in vitro model of BPH consisting in transferring BPH-1-cell-conditioned media to human endothelial H5V cells. Indeed, PWE was able to reduce tube formation in H5V cells through VEGF level reduction even at low concentrations. Overall, we confirmed that inhibition of angiogenesis may be an alternative therapeutic option to prevent neovascularization in prostate tissue with BPH and its transformation into malignant prostate cancer.


Assuntos
Punica granatum , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/patologia , Próstata/patologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/farmacologia , Células Epiteliais/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
2.
Int J Mol Sci ; 24(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37373341

RESUMO

Several studies have highlighted the ability of snail mucus in maintaining healthy skin conditions due to its emollient, regenerative, and protective properties. In particular, mucus derived from Helix aspersa muller has already been reported to have beneficial properties such as antimicrobial activity and wound repair capacity. In order to enhance the beneficial effects of snail mucus, a formulation enriched with antioxidant compounds derived from edible flower waste (Acmella oleracea L., Centaurea cyanus L., Tagetes erecta L., Calendula officinalis L., and Moringa oleifera Lam.) was obtained. UVB damage was used as a model to investigate in vitro the cytoprotective effects of snail mucus and edible flower extract. Results demonstrated that polyphenols from the flower waste extract boosted the antioxidant activity of snail mucus, providing cytoprotective effects in keratinocytes exposed to UVB radiation. Additionally, glutathione content, reactive oxygen species (ROS), and lipid peroxidation levels were reduced following the combined treatment with snail mucus and edible flower waste extract. We demonstrated that flower waste can be considered a valid candidate for cosmeceutical applications due to its potent antioxidant activity. Thus, a new formulation of snail mucus enriched in extracts of edible flower waste could be useful to design innovative and sustainable broadband natural UV-screen cosmeceutical products.


Assuntos
Antioxidantes , Cosmecêuticos , Antioxidantes/farmacologia , Antioxidantes/análise , Cosmecêuticos/farmacologia , Extratos Vegetais/química , Queratinócitos , Flores/química , Muco/química , Raios Ultravioleta/efeitos adversos
3.
Molecules ; 26(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361563

RESUMO

The consumption of plant-based food is important for health promotion, especially regarding the prevention and management of chronic diseases such as diabetes. We investigated the effects of a lemon extract (LE), containing ≥20.0% total flavanones and ≥1.0% total hydroxycinnamic acids, on insulin signaling in murine 3T3-L1 adipocytes treated with TNF-α, which was used to mimic in vitro the insulin resistance condition that characterizes diabetes mellitus. Our results showed LE increased PPARγ, GLUT4 and DGAT-1 levels, demonstrating the potential of this lemon extract in the management of insulin resistance conditions associated with TNF-α pathway activation. LE treatment further decreased the release of interleukin 6 (IL-6) and restored triglyceride synthesis, which is the main feature of a healthy adipocyte.


Assuntos
Adipócitos/metabolismo , Citrus/química , Resistência à Insulina , Compostos Fitoquímicos , Extratos Vegetais , Fator de Necrose Tumoral alfa/efeitos adversos , Células 3T3-L1 , Animais , Camundongos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
4.
Nat Prod Res ; 35(23): 5378-5383, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32441543

RESUMO

Several natural products have been reported to be involved in the suppression of adipogenesis. In this study, we reveal that a bergamot extract (BE) decreased the accumulation of intracellular lipids in murine pre-adipocytes 3T3-L1 cells during adipogenic differentiation. Both the inhibition of HMG-CoA reductase activity and the differentiation and proliferation of adipocytes could be used as a strategy for the treatment and prevention of obesity. The results of this study show a reduction of HMG-CoA activity and of lipid droplet accumulation in the presence of the BE, suggesting the potential of BE as an anti-adipogenic agent to lower the content of cholesterol and body fat and prevent a gain in body weight. Moreover, BE as the result of high percentages of flavonoid compounds such as neoriocitrin, naringin and neohesperidin, the main flavonoids contained in BE, led to significant inhibition of DPPH free radical, demonstrating a strong radical scavenging activity.


Assuntos
Fármacos Antiobesidade , Flavonoides , Células 3T3-L1 , Animais , Diferenciação Celular , Colesterol , Flavonoides/farmacologia , Lipídeos , Camundongos , Extratos Vegetais/farmacologia
5.
Nat Prod Res ; 35(22): 4774-4778, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32009451

RESUMO

Lemon fruit is a source of bioactive compounds, which has many beneficial effects on health. Obesity is characterized by over-accumulation of adipose tissue as a result of increased adipocyte size and number. Adipogenesis is mediated and assisted by various transcription factors that induce lipid-metabolizing enzymes followed by an increase of perilipin expression and lipid droplets generation. Here, we evaluate the effect of lemon extract (LE) as radical scavenger and the consequent regulation of adipocyte differentiation and lipid accumulation. 3T3-L1 murine pre-adipocytes were differentiated and treated with different LE concentrations. The high percentages of flavonoid contained in LE led to a significant inhibition of DPPH radical and reactive oxygen species, demonstrating a strong radical scavenger activity. Treatment of 3T3-cells with LE showed a significant decrease of perilipin expression, subsequently confirmed by the reduction of lipid droplet accumulation, resulting from Oil Red O Staining and by the downregulation of PPARγ and DGAT-1mRNA.


Assuntos
Adipócitos , Flavonoides , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Diferenciação Celular , Flavonoides/farmacologia , Metabolismo dos Lipídeos , Camundongos , PPAR gama/metabolismo , Extratos Vegetais/farmacologia
6.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751794

RESUMO

AIM: Obesity is associated with metabolic syndrome, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. In this study, we investigated whether the dietary supplementation of pomegranate seed oil (PSO) exerted a protective effect on liver lipid uptake, fibrosis, and mitochondrial function in a mouse model of obesity and insulin resistance. METHOD: In this in vivo study, eight-week-old C57BL/6J male mice were fed with a high fat diet (HFD) for 24 weeks and then were divided into three groups as follows: group (1) Lean; group (n = 6) (2) HF diet; group (n = 6) (3) HF diet treated with PSO (40 mL/kg food) (n = 6) for eight additional weeks starting at 24 weeks. Physiological parameters, lipid droplet accumulation, inflammatory biomarkers, antioxidant biomarkers, mitochondrial biogenesis, insulin sensitivity, and hepatic fibrosis were determined to examine whether PSO intervention prevents obesity-associated metabolic syndrome. RESULTS: The PSO group displayed an increase in oxygen consumption, as well as a decrease in fasting glucose and blood pressure (p < 0.05) when compared to the HFD-fed mice group. PSO increased both the activity and expression of hepatic HO-1, downregulated inflammatory adipokines, and decreased hepatic fibrosis. PSO increased the levels of thermogenic genes, mitochondrial signaling, and lipid metabolism through increases in Mfn2, OPA-1, PRDM 16, and PGC1α. Furthermore, PSO upregulated obesity-mediated hepatic insulin receptor phosphorylation Tyr-972, p-IRB tyr1146, and pAMPK, thereby decreasing insulin resistance. CONCLUSIONS: These results indicated that PSO decreased obesity-mediated insulin resistance and the progression of hepatic fibrosis through an improved liver signaling, as manifested by increased insulin receptor phosphorylation and thermogenic genes. Furthermore, our findings indicate a potential therapeutic role for PSO in the prevention of obesity-associated NAFLD, NASH, and other metabolic disorders.


Assuntos
Antioxidantes/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Obesidade/tratamento farmacológico , Óleos de Plantas/uso terapêutico , Animais , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Mitocôndrias/patologia , Punica granatum/química , Sementes/química
7.
Int J Mol Sci ; 20(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261958

RESUMO

Natural bioactive compounds may be used in obese patients because of their ability to impact on various key mechanisms involved in the complex pathophysiological mechanisms of such condition. The aim of this study was to investigate the effect of a Mangifera indica L. leaf extract (MLE) on adipogenic differentiation of murine preadipocyte cells. 3T3-L1 cells were treated during their differentiation with various concentrations of (Mangifera indica L.) leaves extract (MLE) (750, 380, 150, 75 and 35 µg) in order to assess their lipid content, adiponectin production, expression profile of genes involved in lipid metabolism, oxidative stress and inflammation. Our results showed that MLE was particularly enriched in polyphenols (46.30 ± 0.083 mg/g) and that pharmacological treatment of cells resulted in a significant increase of adiponectin levels and reduction of intracellular lipid content. Consistently with these results, MLE resulted in a significant decrease of the expression of genes involved in lipid metabolism (FAS, PPARG, DGAT1, DGAT2, and SCD-1). In conclusion, our results suggest that MLE may represent a possible pharmacological tool for obese or metabolic syndrome patients.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia , Adiponectina/metabolismo , Antioxidantes/farmacologia , Mangifera/química , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Antioxidantes/química , Metabolismo dos Lipídeos , Camundongos , Estresse Oxidativo , Extratos Vegetais/química , Folhas de Planta/química , Polifenóis/análise , Xantonas/análise
8.
Artigo em Inglês | MEDLINE | ID: mdl-30416532

RESUMO

Recent experimental data suggest that fatty acids and lipotoxicity could play a role in the initiation and evolution of metabolic bone diseases such as osteoporosis. A functional bone marrow adipose tissue (BMAT) may provide support to surrounding cells and tissues or may serve as a lipid reservoir that protects skeletal osteoblasts from lipotoxicity. The present study examined the effect of N-acetylcysteine (NAC), a powerful antioxidant and precursor of glutathione, commonly used to treat chronic obstructive pulmonary disease, on triglycerides accumulation in bone marrow stromal cells-derived adipocytes. Quantification of Oil Red O stained cells showed that lipid droplets decreased following NAC treatment. Additionally, exposure of bone marrow stromal cells (HS-5) to NAC increased adiponectin, PPARγ, HO-1, and SIRT-1 and increased beta-oxidation markers such as PPARα and PPARδ mRNA levels. As there is now substantial interest in alternative medicine, the observed therapeutic value of NAC should be taken into consideration in diabetic patients.

9.
Curr Med Chem ; 25(13): 1577-1595, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28618991

RESUMO

BACKGROUND: The aim of this review is to summarize the effects of various naturally occurring polyphenols in the management of metabolic dysfunctions. This cluster of metabolic abnormalities comprises insulin resistance, increased levels of free fatty acids, hypercholesterolemia, obesity, hyperglycemia and hypertension, diabetes mellitus (DM) type 1 (T1DM) and type 2 (T2DM) along with DM-induced complications. Most of them are included in the well-known metabolic syndrome (MS). These metabolic dysfunctions in turn are tightly associated to a high risk of development of cardiovascular diseases. Although molecular mechanisms underlying the onset of metabolic dysfunctions and related complications are not yet clear, it is widely recognized that they are associated to oxidative stress and chronic low-grade of inflammatory levels. METHODS: We undertook a structured search of bibliographic references through the use of SciFinder. The database was provided by a division of ACS (American Chemical Society) and guarantees access to the world's most extensive and authoritative source of references. The search was performed using "heme oxygenase-1" as research topic and a subsequent refinement was done by using inclusion/exclusion criteria. The quality of retrieved papers was evaluated on the basis of standard tools. RESULTS: From a careful review of the selected literature, of interest, the use of natural antioxidant polyphenols seems to be the ideal pharmacological treatment since they are endowed with strong antioxidant and anti-inflammatory properties. In particular, some polyphenols such as curcumin, quercetin, genistein, and caffeic acid phenethyl ester are able to potently activate nuclear factor erythroid 2-related factor 2 (Nrf2) and related downstream expression of enzymes such as heme oxygenase-1 (HO-1). Indeed, an overexpression of HO-1 has been demonstrated to play a beneficial role in metabolic diseases. CONCLUSION: The following review is intended to stimulate interest in the role of natural occurring HO-1 inducers in metabolic dysfunction, focusing on the clinical potential of HO-1 activity to restore the balance between pro-oxidant and anti-oxidants systems.


Assuntos
Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Doenças Metabólicas/tratamento farmacológico , Polifenóis/uso terapêutico , Animais , Doenças Cardiovasculares/metabolismo , Indução Enzimática , Humanos , Doenças Metabólicas/metabolismo , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
10.
Oncol Rep ; 36(4): 2298-304, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27573437

RESUMO

Cancers of the digestive tract, in particular colorectal cancer (CRC), are among those most responsive to dietary modification. Research has shown that approximately 75% of all sporadic cases of CRC are directly influenced by diet. Many natural compounds have been investigated for their potential usefulness as cancer chemopreventive agents as they have been thought to suppress carcinogenesis mainly during the initiation phase due to their radical scavenger activity. Since there is an increasing interest in the in vivo protective effects of natural compounds contained in plants against oxidative damage involved in several human diseases such as cancer, the aim of the present research was to test the effects of a Celtis aetnensis (Tornab.) Strobl twig extract on a human colon carcinoma cell line (Caco2). In order to elucidate the mechanisms of action of this extract, LDH release, GSH content, ROS levels, caspase-3 and γ-GCS expression were also evaluated. The results revealed that the Celtis aetnensis extract reduced the cell viability of the Caco2 cells inducing apoptosis at the lowest concentration and necrosis at higher dosages. In addition, this extract caused an increase in the levels of ROS, a decrease in RSH levels and in the expression of HO-1. The expression of γ-GCS was not modified in the Celtis aetnensis-treated Caco-2 cells. These results suggest an interference of this extract on the oxidant/antioxidant cell balance with consequent cell damage. The present study supports the growing body of data suggesting the bioactivities of Celtis aetnensis (Tornab.) Strobl and its potential impact on cancer therapy and on human health.


Assuntos
Antioxidantes/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Proteínas de Neoplasias/biossíntese , Extratos Vegetais/administração & dosagem , Antioxidantes/química , Apoptose/efeitos dos fármacos , Células CACO-2 , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Ulmaceae/química
11.
PLoS One ; 10(4): e0122320, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25848759

RESUMO

Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae) is widely used in traditional medicine. There is increasing interest on the in vivo protective effects of natural compounds contained in plants against oxidative damage caused from reactive oxygen species. In the present study the total phenolic and flavonoid contents of aqueous, methanol and dichloromethane extracts of leaves of Tithonia diversifolia (Hemsl.) A. Gray were determined; furthermore, free radical scavenging capacity of each extract and the ability of these extracts to inhibit in vitro plasma lipid peroxidation were also evaluated. Since oxidative stress may be involved in trasformation of pre-adipocytes into adipocytes, to test the hypothesis that Tithonia extract may also affect adipocyte differentiation, human mesenchymal stem cell cultures were treated with Tithonia diversifolia aqueous extract and cell viability, free radical levels, Oil-Red O staining and western bolt analysis for heme oxygenase and 5'-adenosine monophoshate-activated protein kinase were carried out. Results obtained in the present study provide evidence that Tithonia diversifolia (Hemsl.) A. Gray exhibits interesting health promoting properties, resulting both from its free radical scavenger capacity and also by induction of protective cellular systems involved in cellular stress defenses and in adipogenesis of mesenchymal cells.


Assuntos
Adipócitos/metabolismo , Asteraceae/química , Sequestradores de Radicais Livres/farmacologia , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adipócitos/citologia , Diferenciação Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/química , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Extratos Vegetais/química
12.
Angiology ; 66(9): 856-61, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25632052

RESUMO

The impact of a natural supplement (Kepar; Rikrea, Italy), containing several plant extracts such as curcuma longa, silymarin, guggul, chlorogenic acid, and inulin, was evaluated in 78 patients with metabolic syndrome (MetS; 45 men; age: 62 ± 9 years). Kepar at a dose of 2 pills/d was given for 4 months as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study. Anthropometric variables, plasma lipids, glucose parameters, and oxidative stress were measured at baseline and after 4 months. We found significant reductions in body weight (from 81.1 ± 13.5 to 79.4 ± 12.5 kg, P < .0001), body mass index (from 29.6 [23.7] to 29.3 [21.9] kg/m(2), P = .001), and waist circumference (from 105 ± 11 to 102 ± 10 cm, P = .0004) as well as in fasting glucose (from 6.5 [11.7] to 6.4 [7.6] mmol/L, P = .014) and total cholesterol (from 4.8 ± 1.4 to 4.5 ± 1.0 mmol/L, P = .03). No significant changes were found in the other appraised parameters, including oxidative stress. In conclusion, after few months of treatment Kepar seems to exert beneficial effects in patients with MetS. Larger studies with a longer follow-up period are needed to confirm these preliminary findings.


Assuntos
Ácido Clorogênico/uso terapêutico , Curcuma , Suplementos Nutricionais , Inulina/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Gomas Vegetais/uso terapêutico , Silimarina/uso terapêutico , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Ácido Clorogênico/efeitos adversos , Colesterol/sangue , Commiphora , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Inulina/efeitos adversos , Itália , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Projetos Piloto , Extratos Vegetais/efeitos adversos , Gomas Vegetais/efeitos adversos , Plantas Medicinais , Silimarina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos
13.
Urology ; 83(6): 1444.e7-13, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24862399

RESUMO

OBJECTIVE: To investigate the role of heme oxygenase (HO) system in moderate to severe benign prostatic hyperplasia and lower urinary tract symptom patients and the influence of metabolic syndrome (MetS) components on HO-1 or HO-2 prostatic levels. METHODS: One hundred thirty-two consecutive patients who underwent transurethral resection of the prostate were prospectively enrolled. MetS was defined by the International Diabetes Federation. Patients were divided in 2 groups: group A (high-density lipoprotein-cholesterol [HDL-C]≥40 mg/dL and triglycerides<150 mg/dL) and group B (HDL-C<40 mg/dL and triglycerides≥150 mg/dL). Surgical specimens were collected for HO level determination. HO-1 levels were determined by enzyme-linked immunosorbent assay and HO-1 levels by Western blotting. RESULTS: Patients with MetS showed lower levels of HO-1 (5.29 vs 6.28 ng/mL; P=.04), HO-2 (1.01 vs 1.83 ng/mL; P=.04), phosphorylated activated protein kinase (pAMPK; 0.62 vs 1.11 AUI; P<.01), and HO-activity (61.43 vs 70.22 AUI; P<.01) with respect to normal. The Pearson correlation analysis showed that HO-1, HO-2, and HO activity were negatively associated with waist circumference (P<.05), body mass index (P<.05), triglycerides (P<.05) and positively with HDL-C (P<.05). Group B showed lower levels of HO-1 (4.7 vs 6.6 ng/mL; P<.05), HO-2 (1.4 vs 0.4 ng/mL; P=.03), HO-activity (69.63 vs 58.42 AUI; P=.04), and higher International Prostate Symptoms Score (21.4 vs 25.0; P<.05) with respect to group A. The enzyme-linked immunosorbent assay showed that HO-1 and HO activity levels were significantly lower in group B compared with group A. Reduced HDL-C and elevated triglyceride levels decreased HO-1 expression in the prostate tissue. Western blot analysis of tissue samples showed significant differences in basal protein expression levels of HO-2 and pAMPK in group B compared with group A. CONCLUSION: Alteration of serum triglycerides and HDL-C significantly impairs HO-1 and HO-2 levels in benign prostatic hyperplasia patients.


Assuntos
Heme Oxigenase (Desciclizante)/sangue , Sintomas do Trato Urinário Inferior/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Triglicerídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Western Blotting , HDL-Colesterol/sangue , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Humanos , Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/patologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Sensibilidade e Especificidade , Ressecção Transuretral da Próstata/métodos
14.
Molecules ; 18(3): 3241-9, 2013 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-23486103

RESUMO

Momordica foetida Schumach. et Thonn. (Cucurbitaceae) is a perennial climbing herb with tendrils, found in swampy areas in Central Uganda. Antidiabetic and antilipogenic activities were reported for some Momordica species, however the mechanism of action is still unknown. Oxidative stress may represent an important pathogenic mechanism in obesity-associated metabolic syndrome. The present study evaluated free radical scavenging capacity of different concentrations of aqueous, methanolic and dichloromethane leaf extracts of Momordica foetida Schumach. et Thonn. and the ability of these extracts to inhibit in vitro plasma lipid peroxidation; in addition, healthy human adipose mesenchymal stem cell cultures were used in order to test the hypothesis that these extracts may affect adipocyte differentiation. Results obtained in this study suggested that aqueous extract might be useful in preventing metabolic syndrome.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Momordica/química , Extratos Vegetais/química , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Flavonoides/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Folhas de Planta/química , Polifenóis/química , Superóxidos/antagonistas & inibidores
15.
Curr Pharm Des ; 19(15): 2765-70, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23092325

RESUMO

Identification of imatinib mesylate as a potent inhibitor of the Abl kinase and the subsequent findings that this compound displays growth inhibitory and pro-apoptotic effects in Bcr-Abl+ cells, has deeply conditioned CML treatment. Unfortunately the initial striking efficacy of this drug has been overshadowed by the development of clinical resistance. A wide variety of molecular mechanisms can underlie such resistance mechanisms. In the recent years, heme oxygenase-1 (HO-1) expression has been reported as an important protective endogenous mechanism against physical, chemical and biological stress and this cytoprotective role has already been demonstrated for several solid tumors and acute leukemias. The aim of the present study was to investigate the effect of HO-1 expression on cell proliferation and apoptosis in chronic myeloid leukemia cells, K562 and LAMA-84 cell lines following imatinib treatment. Cells were incubated for 24h with Imatinib (1 µM) alone or in combination with Hemin (10µM), an inducer of HO-1. In addition, cells were also treated with HO byproducts, bilirubin and carbon monoxide (CO), or with a protease inhibitor (Ed64) to inhibit HO-1 nuclear translocation. Pharmacological induction of HO-1 was able to overcome the effect of imatinib. The cytoprotective effect of HO-1 was further confirmed after silencing HO-1 by siRNA. Interestingly, neither bilirubin nor CO was able to protect cells from Imatinib-induced toxicity. By contrast, the protective effect of HO-1 was mitigated by the addition of E64d, preventing HO-1 nuclear translocation. Finally, imatinib was able to increase the formation of cellular reactive oxygen species (ROS) and this effect was reversed by HO-1 induction or the addition of N-acetylcisteine (NAC). In conclusion, the protective effect of HO-1 on imatinib-induced cytotoxicity does not involve its enzymatic byproducts, but rather the nuclear translocation of HO-1 following proteolytic cleavage.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Núcleo Celular/metabolismo , Heme Oxigenase-1/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Inativação Gênica , Heme Oxigenase-1/genética , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Espécies Reativas de Oxigênio/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-23008739

RESUMO

This study investigated the effect of cyanidin-3-O-ß-glucoside on an experimental model of partial/transient cerebral ischemia in the rats in order to verify the effectiveness of both pre- and posttreatments. Cyanidin-3-O-ß-glucoside-pretreated rats were injected with 10 mg/Kg i.p. 1 h before the induction of cerebral ischemia; in posttreated rats, the same dosage was injected during reperfusion (30 min after restoring blood flow). Cerebral ischemia was induced by bilateral clamping of common carotid arteries for 20 min. Ischemic rats were sacrificed immediately after 20 min ischemia; postischemic reperfused animals were sacrificed after 3 or 24 h of restoring blood flow. Results showed that treatment with cyanidin increased the levels of nonproteic thiol groups after 24 h of postischemic reperfusion, significantly reduced the lipid hydroperoxides, and increased the expression of heme oxygenase and γ-glutamyl cysteine synthase; a significant reduction in the expression of neuronal and inducible nitric oxide synthases and the equally significant increase in the endothelial isoform were observed. Significant modifications were also detected in enzymes involved in metabolism of endogenous inhibitors of nitric oxide. Most of the effects were observed with both pre- and posttreatments with cyanidin-3-O-ß-glucoside suggesting a role of anthocyanin in both prevention and treatment of postischemic reperfusion brain damage.

17.
J Med Food ; 12(1): 145-50, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19298208

RESUMO

Aerobic exercise increases free radical production as a consequence of enhanced oxygen consumption. If free radical formation exceeds antioxidant capacity, lipids, proteins, and DNA may be oxidized. Oxidative stress is widely recognized as a factor in many degenerative human diseases. The role of dietary antioxidants in protection against disease is a topic of continuing interest. In fact, there is epidemiological evidence correlating a higher intake of nutrients possessing antioxidant abilities with a lower incidence of various human diseases. This study was directed at investigating whether changes in plasma antioxidant capacity and oxidative stress markers occur in voluntary wheel runners, before and after oral supplementation with lycopene and isoflavones. For this purpose, plasma antioxidant capacity and oxidative stress markers were assessed in long distance runners at the end of a 60-minute run. Comparisons were made between runners before and after 60 days of supplementation with lycopene and isoflavones. DNA damage in blood cells of the same samples was also evaluated by comet assay. This investigation shows that oral supplementation with lycopene and soy-derived isoflavones significantly reduced lipid peroxidation and enhanced plasma nonproteic antioxidant defense.


Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Exercício Físico/fisiologia , Isoflavonas/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Corrida/fisiologia , Idoso , Antioxidantes/metabolismo , Dano ao DNA , Suplementos Nutricionais , Humanos , Peróxidos Lipídicos/sangue , Licopeno , Solanum lycopersicum , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/farmacologia , Glycine max , Compostos de Sulfidrila/sangue
18.
Br J Nutr ; 100(1): 27-35, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18053307

RESUMO

Anthocyanins are a class of flavonoids, widely spread throughout the plant kingdom, exhibiting important antioxidant and anti-inflammatory actions as well as chemotherapeutic effects; nonetheless, little is known about the molecular mechanisms by which these activities are exerted. The present study is aimed at investigating molecular mechanisms involved in the chemotherapeutic effects induced by both cyanidin-3-O-beta glucopyranoside (CY3G) and its aglycon form, cyanidin chloride (CY), in human colon cancer cells (CaCo2). The effect on cell growth, reactive oxygen species (ROS) formation and cell cycle/stress proteins modification, including ataxia teleangectasia mutated protein (ATM), p53, p21, 8-oxoguanine DNA glycosylase (OGG1), 70 kDa heat shock protein (HSP70) and topoisomerase IIbeta, as well as on DNA fragmentation, was determined. CY and CY3G treatment affect cell growth and cell proliferation, this latter in a moderately dose-dependent way. Interestingly, ROS level is decreased by any concentration of CY and, only at the lowest concentration, by CY3G. Moreover, the two molecules exert their activities increasing ATM, topoisomerase II, HSP70 and p53 expression. The analysis of DNA fragmentation by Comet assay evidences: (1) a dose-dependent increase in DNA damage only after treatment with CY3G; (2) a more evident trend in the DNA fragmentation when the treatment is performed on agarose embedded cells (cellular atypical Comet); (3) a highly dose-dependent DNA fragmentation induced by CY when the treatment is carried out on agarose embedded naked DNA (acellular atypical Comet). The present findings substantiate a possible chemotherapeutic role of anthocyanins and suggest that CY and CY3G act on CaCo2 by different mechanisms, respectively, ROS-dependent and ROS-independent.


Assuntos
Antocianinas/farmacologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias do Colo/patologia , Dano ao DNA , Antineoplásicos , Células CACO-2 , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Ensaio Cometa/métodos , DNA de Neoplasias/genética , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Humanos , Proteínas de Neoplasias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
19.
J Med Food ; 10(4): 650-6, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18158836

RESUMO

The profile of phenolic compounds, antioxidant capacity, oxidative stability, and chemical characteristics (free acidity, peroxide value, specific extinction K232 and K270 values, and DeltaK) of 22 commercial extra virgin olive oil (EVOO) samples coming from the denomination of protected origin (DPO) Monti Iblei and obtained from olives harvested in the period September-December 2005 in the production area of the province of Siracusa (Sicily, Italy) were evaluated. The content of total phenols, expressed as gallic acid equivalents, ranged from 14.80 to 121.20 mg/100 g, with a mean value of 53.72 mg/100 g, mainly attributable to deacetoxyligstroside aglycone, deacetoxyoleuropein aglycone, oleuropein aglycone, and ligstroside aglycone. The mean values of Trolox equivalent antioxidant capacity (TEAC) and of oxidative stability were 54.76 and 11.99 hours, respectively. Both TEAC and oxidative stability were positively correlated to the phenol content and to the percentage of inclusion of the olive cultivar "Tonda Iblea." The high mean content of phenols, besides conferring prolonged oxidative stability, likely confers to the DPO Monti Iblei EVOO marked potential beneficial effects for human health.


Assuntos
Antioxidantes/análise , Fenóis/análise , Óleos de Plantas/química , Aldeídos/análise , Monoterpenos Ciclopentânicos , Estabilidade de Medicamentos , Ácido Gálico/análise , Concentração de Íons de Hidrogênio , Olea/crescimento & desenvolvimento , Azeite de Oliva , Oxirredução , Peróxidos/análise , Estações do Ano
20.
J Ethnopharmacol ; 100(3): 323-32, 2005 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-15941635

RESUMO

Geum quellyon Sweet, a perennial herb of the Rosaceae family, has been used in the traditional medicine of the Mapuche Amerindians of Chile to treat tooth neuralgia, gastric inflammation, prostatitis and to regulate menstruation, and for its diuretic and aphrodisiac properties. Although many benefits have been claimed for this plant, few scientific studies are available in the literature. In this study, we investigated the antioxidant activity of a methanolic extract of Geum quellyon roots. We also examined the anticancer action of this plant on Caco-2 (colon adenocarcinoma cells), DU-145 (androgen-insensitive prostate cancer cells) and KB (oral squamous carcinoma cells) human tumor cell lines. Our data showed that Geum quellyon extract, containing tannins, exhibits interesting antioxidant properties, expressed by its capacity to scavenge 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and superoxide anion (O(2)*-), to inhibit xanthine oxidase activity, to chelate metals, and to protect plasmid DNA from cleavage induced by hydroxyl radicals (*OH) and nitric oxide (NO). These results may explain, at least in part, its use in Mapuche traditional medicine for gastric inflammation and prostatitis. The assays on human tumor cell lines demonstrated that this natural product exhibits a inhibitory effect on all human cancer cells examined, and seem to indicate that necrosis cell death is triggered in KB cells and Caco-2, while apoptotic cell demise appears to be induced in DU-145. The effect evidenced in Caco-2 cells can be in part correlated to a modulation of redox-sensitive mechanisms.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Geum/química , Compostos de Bifenilo/química , Células CACO-2 , Linhagem Celular Tumoral , Quelantes/química , Quelantes/farmacologia , Chile , Ensaio Cometa , DNA de Neoplasias/biossíntese , DNA de Neoplasias/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Humanos , Hidrazinas/química , Peróxido de Hidrogênio/química , Células KB , L-Lactato Desidrogenase/metabolismo , Masculino , Medicina Tradicional , Picratos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Taninos/química , Taninos/isolamento & purificação , Taninos/farmacologia , Sais de Tetrazólio , Tiazóis , Raios Ultravioleta , Xantina Oxidase/antagonistas & inibidores
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