RESUMEN
Diabetes mellitus is a public health concern, affecting 10.5% of the population. Protocatechuic acid (PCA), a polyphenol, exerts beneficial effects on insulin resistance and diabetes. This study investigated the role of PCA in improving insulin resistance and the crosstalk between muscle with liver and adipose tissue. C2C12 myotubes received four treatments: Control, PCA, insulin resistance (IR), and IR-PCA. Conditioned media from C2C12 was used to incubate HepG2 and 3T3-L1 adipocytes. The impact of PCA was analyzed on glucose uptake and signaling pathways. PCA (80 µM) significantly enhanced glucose uptake in C2C12, HepG2, and 3T3-L1 adipocytes (p < 0.05). In C2C12, PCA significantly elevated GLUT-4, IRS-1, IRS-2, PPAR-γ, P-AMPK, and P-Akt vs. Control (p ≤ 0.05), and modulated pathways in IR-PCA. In HepG2, PPAR-γ and P-Akt increased significantly in Control (CM) vs. No CM, and PCA dose upregulated PPAR-γ, P-AMPK, and P-AKT (p < 0.05). In the 3T3-L1 adipocytes, PI3K and GLUT-4 expression was elevated in PCA (CM) vs. No CM. A significant elevation of IRS-1, GLUT-4, and P-AMPK was observed in IR-PCA vs. IR (p ≤ 0.001). Herein, PCA strengthens insulin signaling by activating key proteins of that pathway and regulating glucose uptake. Further, conditioned media modulated crosstalk between muscle with liver and adipose tissue, thus regulating glucose metabolism.
Asunto(s)
Resistencia a la Insulina , Ratones , Animales , Medios de Cultivo Condicionados/farmacología , Medios de Cultivo Condicionados/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Tejido Adiposo/metabolismo , Insulina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Hígado/metabolismo , Glucosa/metabolismo , Células 3T3-L1RESUMEN
Lactoferrin (LF) is a milk protein that may be an interesting candidate for the antidiabetic properties of milk due to its well-documented bioactivity and implication in diabetes. Here, we investigated the functional action of LF purified from camel and bovine milk (cLF, bLF) on insulin receptors (IR) and their pharmacology and signaling in hepatocarcinoma (HepG2) and human embryonic kidney (HEK293) cells. For this, we examined IR activation by bioluminescence resonance energy transfer (BRET) technology and the phosphorylation of its key downstream signaling kinases by western blot. The purified cLF and bLF induced phosphorylation of IR, AKT, and ERK1/2 in HepG2 and HEK293 cells. The BRET assays in HEK293 cells confirm the pharmacological action of cLF and bLF on IR, with a possible allosteric mode of action. This reveals for the first time the bioactivity of LF toward IR function, indicating it as a potential bioactive protein behind the antidiabetic properties of camel milk.
Asunto(s)
Camelus , Lactoferrina , Receptor de Insulina , Animales , Camelus/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Lactoferrina/metabolismo , Sistema de Señalización de MAP Quinasas , Leche , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor de Insulina/metabolismoRESUMEN
The objective of this study was to assess protein degradation and biological activities of the water-soluble extract (WSE) and the 10 kDa permeable and nonpermeable fractions of in vitro digesta of low-fat Akawi cheese made from blends (100:0, 85:15, or 70:30) of bovine milk and camel milk and ripened for 28 d. Biological activities, such as antioxidant activities, amylase and glucosidase inhibition, angiotensin-converting enzyme inhibition, and antiproliferative of the WSE, and the 10 kDa permeable and nonpermeable fraction of the digesta were assessed. To identify the nature of the bioaccessible compounds, untargeted metabolomic analysis was carried out by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Higher o-phthaldialdehyde absorbances were observed in cheeses made of bovine-camel milk blends compared with cheese from bovine milk only. The WSE from these blends also exhibited higher angiotensin-converting enzyme inhibitory effects and higher antiproliferative effects than from bovine milk. The results from this study suggest that the use of blends of camel milk and bovine milk can modulate biological activities of low-fat Akawi cheese.
Asunto(s)
Queso , Animales , Antioxidantes , Camelus , Bovinos , Queso/análisis , Digestión , Manipulación de Alimentos , LecheRESUMEN
This study aimed to investigate in vitro anticancer activity by antiproliferative activity, antihypertensive activity by angiotensin-converting enzyme inhibition, antidiabetic activity by α-amylase and α-glucosidase inhibitions, and antioxidant activities of camel milk fermented with camel milk probiotic compared with fermented bovine milk. The camel milk probiotic strain Lactococcus lactis KX881782 (Lc.K782) and control Lactobacillus acidophilus DSM9126 (La.DSM) were used to prepare fermented camel and bovine milks separately. The proteolytic activities of water-soluble extract (WSE) in all fermented camel milk were higher than those in fermented bovine milk. The α-glucosidase inhibitions in both milk types fermented by Lc.K782 ranged from 30 to 40%. Camel milk fermented by Lc.K782 had the highest antioxidant activity by 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulphonic acid). The highest angiotensin-converting enzyme inhibition of WSE in camel milk fermented by Lc.K782 was >80%. The proliferations of Caco-2, MCF-7, and HELA cells were more inhibited when treated with WSE of fermented camel milk extracts.
Asunto(s)
Antihipertensivos/farmacología , Antineoplásicos/farmacología , Antioxidantes/metabolismo , Hipoglucemiantes/farmacología , Lactococcus lactis/química , Leche/química , Animales , Células CACO-2 , Camelus , Bovinos , Proliferación Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Fermentación , Células HeLa , Humanos , Lactobacillus acidophilus/química , Células MCF-7 , Leche/microbiología , Probióticos/administración & dosificación , Probióticos/farmacologíaRESUMEN
Lactic acid bacteria isolated from camel milk exhibit remarkable probiotic and exopolysaccharide (EPS)-producing characteristics. The health-promoting benefits of exopolysaccharide-producing probiotic Lactobacillus plantarum isolated from camel milk used for making low-fat akawi cheese were investigated. Three low-fat akawi cheeses were made using traditional culture (non-EPS-producing, EPS-), commercial EPS-producing (MEPS+), and camel milk EPS-producing (CEPS+) cultures. α-Amylase and α-glucosidase inhibitory activities, antioxidant activities, angiotensin-converting enzyme (ACE) inhibition, and antiproliferative activity were determined. Cheese made with CEPS+ culture exhibited comparable α-amylase inhibition to that of cheeses made with MEPS+. Scavenging rates of cheese made with EPS+ cultures were higher than those of cheese made with EPS- cultures. The percentage of α-glucosidase inhibition ranged from >45% at 0 d to â¼55% at 21 d of storage. After 7 d of storage, the scavenging rate in CEPS+ cheese increased >60% by ABTS assay [2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid)] and >20% by DPPH assay (1,1-diphenyl-2-picrylhydrazyl). Throughout storage, cheese made with EPS+ cultures showed higher ACE-inhibition activity compared with EPS- cultures. Cheese made with CEPS+ showed ACE inhibition >70% after 7 d of storage. Antiproliferation activity of CEPS+ cheese increased from 38 to 48% during 7 d of storage and was maintained above 45% with prolonged storage. Low-fat akawi cheese produced with these cultures exhibited similar or greater health-promoting benefits compared with cheese made using commercial starter cultures. Therefore, incorporation of these cultures in food is promising for commercial uses.
Asunto(s)
Queso , Lactobacillus plantarum/metabolismo , Leche/microbiología , Polisacáridos Bacterianos/biosíntesis , Animales , Camelus , ProbióticosRESUMEN
Avian cell lines derived from germinal crescent primordial germ cells and gonadal gonocytes with long-term proliferative capacity in vitro and their subsequent rates of colonization and germline transmission are described. In general, male cultures proliferate more rapidly than female cultures although both can be developed into cell lines of >2 × 10(6) cells, at which time, they can be grown indefinitely and a cell bank can be established. All the cell lines injected into embryos transmitted through the germline with the percentage of germline transmission of both male and female cell lines varying from single digits to the high 90s. The derivation of these primordial germ cell and gonadal cell lines and the subsequent robustness of germline transmission validates these cells as suitable for establishment of lines of chickens bearing novel genetic modifications.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Células Germinativas/citología , Gónadas/citología , Animales , Animales Modificados Genéticamente , Forma de la Célula , Células Cultivadas , Embrión de Pollo , Quimera/embriología , Células Madre Embrionarias/citología , Femenino , Masculino , Factores de TiempoRESUMEN
Exopolysaccharides (EPSs) are carbohydrate polymers that can be produced from probiotic bacteria. This study characterized the EPSs from Enterococcus faecium (EPS-LB13) and Streptococcus thermophilus (EPS-MLB10) and evaluated their biological and technological potential. The EPSs had high molecular weight and different monosaccharide compositions. The EPSs exhibited various biological activities at 250 mg/L, such as scavenging free radicals (10 % to 88.8 %), enhancing antioxidant capacity (714 to 2848 µg/mL), inhibiting pathogens (53 % to 74 %), and suppressing enzymes and cancer cells (2 % to 83 %), etc. The EPSs supported the growth of beneficial gut bacteria from Proteobacteria, Bacteroidetes, Firmicutes, and Acinetobacter in fecal fermentation with total Short-chain fatty acids production from 5548 to 6023 PPM. Moreover, the EPSs reduced the gelation time of fermented skimmed bovine milk by more than half. These results suggest that the EPSs from LB13 and MLB10 have promising applications in the dairy and pharmaceutical industries.
RESUMEN
Introduction: The synthesis of nanoparticles using naturally occurring reagents such as vitamins, sugars, plant extracts, biodegradable polymers and microorganisms as reductants and capping agents could be considered attractive for nanotechnology. These syntheses have led to the fabrication of limited number of inorganic nanoparticles. Among the reagents mentioned above, plant-based materials seem to be the best candidates, and they are suitable for large-scale biosynthesis of nanoparticles. Methods: The aqueous extract of Moringa peregrina leaves was used to synthesize silver nanoparticles. The synthesized nanoparticles were characterized by various spectral studies including FT-IR, SEM, HR-TEM and XRD. In addition, the antioxidant activity of the silver nanoparticles was studied viz. DPPH, ABTS, hydroxyl radical scavenging, superoxide radical scavenging, nitric oxide scavenging potential and reducing power with varied concentrations. The anticancer potential of the nanoparticles was also studied against MCF-7 and Caco-2 cancer cell lines. Results: The results showed that silver nanoparticles displayed strong antioxidant activity compared with gallic acid. Furthermore, the anticancer potential of the nanoparticles against MCF-7 and Caco-2 in comparison with the standard Doxorubicin revealed that the silver nanoparticles produced significant toxic effects against the studied cancer cell lines with the IC50 values of 41.59 (Caco-2) and 26.93 (MCF-7) µg/mL. Conclusion: In conclusion, the biosynthesized nanoparticles using M. peregrina leaf aqueous extract as a reducing agent showed good antioxidant and anticancer potential on human cancer cells and can be used in biological applications.
Asunto(s)
Antioxidantes , Tecnología Química Verde , Nanopartículas del Metal , Moringa , Extractos Vegetales , Hojas de la Planta , Plata , Humanos , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Células MCF-7 , Células CACO-2 , Extractos Vegetales/química , Extractos Vegetales/farmacología , Moringa/química , Antioxidantes/farmacología , Antioxidantes/química , Hojas de la Planta/química , Supervivencia Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
Exercise training positively regulates glucose metabolism. This study investigated the impact of training and detraining on glucose metabolism, lipid profiles, and liver enzymes. Twenty-six rats completed an initial 4-week moderate-intense training (T0-T4). Then, the animals were randomly assigned to two groups at the end of week 4: AT4: detraining for 8 weeks; AT8: training for 8 weeks and 4-week detraining. Six animals were sacrificed at T0 and T4, four animals/group at T8, and three/group at T12. The study continued for 12 weeks, and all parameters were assessed at T0, T4, T8, and T12. IPGTT significantly improved after 4 weeks of training (p < 0.01) and was further reduced in AT8 at T8. In AT8, 8-week training significantly reduced total cholesterol at T4 and T12 vs. T0 (p < 0.05), LDL at T4, T8, and T12 vs. T0 (p < 0.01), ALP at T8, T12 vs. T0 (p < 0.01), and increased HDL at T8 and ALT at T8 and T12 vs. T0 (p < 0.05). Triglycerides and hexokinase activity increased significantly at T4 and T8 (p < 0.05) and then decreased at T12 in AT8. Pyruvate and glycogen increased at T12 in AT8 vs. AT4. Eight-week training improved LPL and ATGL expressions. Training positively modulated insulin, glucose metabolism, and lipid profiles, but detraining reduced the benefits associated with the initial training.
Asunto(s)
Glucosa , Ácido Pirúvico , Animales , Masculino , Ratas , Hígado , Ratas Wistar , TriglicéridosRESUMEN
This study investigated the differences in health outcomes associated with ferulic acid (FA) supplementation in animals before the induction of diabetes with streptozotocin (STZ) treatment and post-STZ treatment. 18 male Wistar rats were equally distributed into three groups: groups 1 and 2 received FA (50 mg/kg body weight) supplementation one week before STZ treatment (60 mg/kg body weight, intraperitoneal) and one week after STZ treatment, respectively; group 3 received STZ without FA supplementation. FA supplementation was continued for 12 weeks after STZ treatment. The results indicated no difference in glucose and lipid profile with FA supplementation. However, FA supplementation reduced lipid and protein oxidative damage in the heart, liver and pancreas and increased glutathione in the pancreas. The results indicate that while oxidative damages were positively affected by FA, it was not sufficient to improve metabolic markers of diabetes.
RESUMEN
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta resulting in an irreversible and a debilitating motor dysfunction. Though both genetic and idiopathic factors are implicated in the disease etiology, idiopathic PD comprise the majority of clinical cases and is caused by exposure to environmental toxicants and oxidative stress. Fyn kinase activation has been identified as an early molecular signaling event that primes neuroinflammatory and neurodegenerative events associated with dopaminergic cell death. However, the upstream regulator of Fyn activation remains unidentified. We investigated whether the lipid and tyrosine phosphatase PTEN (Phosphatase and Tensin homolog deleted on chromosome 10) could be the upstream regulator of Fyn activation in PD models as PTEN has been previously reported to contribute to Parkinsonian pathology. Our findings, using bioluminescence resonance energy transfer (BRET) and immunoblotting, indicate for the first time that PTEN is a critical early stress sensor in response to oxidative stress and neurotoxicants in in vitro models of PD. Pharmacological attenuation of PTEN activity rescues dopaminergic neurons from neurotoxicant-induced cytotoxicity by modulating Fyn kinase activation. Our findings also identify PTEN's novel roles in contributing to mitochondrial dysfunction which contribute to neurodegenerative processes. Interestingly, we found that PTEN positively regulates interleukin-1ß (IL-1ß) and the transcription of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Taken together, we have identified PTEN as a disease course altering pharmacological target that may be further validated for the development of novel therapeutic strategies targeting PD.
Asunto(s)
Neuronas Dopaminérgicas , Fosfohidrolasa PTEN , Enfermedad de Parkinson , Humanos , Neuronas Dopaminérgicas/metabolismo , Estrés Oxidativo , Enfermedad de Parkinson/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Transducción de Señal/fisiología , Animales , RatasRESUMEN
Utilising major waste products from the food industry can have both a great environmental impact and be a means to improve consumer health. Date seed is a food industry byproduct that has been proven to have high nutritional value. The aim of this work was to measure the total polyphenolic content (TPC), flavonoids, and antioxidant activity of the seeds of six date fruit varieties, Fard, Khalas, Khinaizi, Sukkary, Shaham, and Zahidi, and to use those seeds to enhance the antioxidant value of cookies by partially substituting flour with ground date seed. Date seed powder (DSP) was extracted at three levels of sample to solvent ratio (5:1, 10:1 and 15:1 mg/mL). Cookies were prepared using three substitution levels of wheat flour (2.5, 5.0, and 7.5%, w/w) by DSP and two types of flour (white and whole wheat), and were baked at two different temperatures, 180 and 200 °C. The composite cookies were found to contain a significant amount of TPC and flavonoids, and showed increased antioxidant activity compared with the control samples.
RESUMEN
In this study, attempts were made to utilize date by-product (date fruit pomace; DFP). This study aimed to investigate the health-promoting benefits of the fermented and non-fermented DFP before in vitro digestion and after (bioaccessible fraction). Untargeted metabolomic analyses for bioaccessible fractions were performed by UPLC-QTOF. DPPH percentages were 89.7%-90.3%, 90.1%-91.3%, and 90.8%-91.3% in the control, I. orientalis, and P. kudriazevii samples, respectively, before digestion; α-glucosidase inhibition before digestion was 1.9%-24.4%, 16.3%-30.0%, and 21.3%-31.3%, respectively; antimicrobial activities were 6.1%-13.3%, 13.7%-25.7%, and 20.6%-28.0% against E. coli O157:H7 and 2.2%-11.9%, 7.2%-20.7%, and 11.9%-29.2% against L. monocytogenes, respectively. The DPPH scavenging percentages were â¼63% lower in the bioaccessible fraction. The differentially regulated metabolites classes were benzene and derivatives, amino acids, peptides and analogs, organic acids, and phenols. This study revealed that the fermented DFP exhibited higher health properties than control.
Asunto(s)
Escherichia coli O157 , Phoeniceae , Antioxidantes/química , Fermentación , Frutas/química , Metabolómica , Fenoles/análisis , Phoeniceae/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
Sphingosine (SPH) is an important bioactive lipid involved in mediating a variety of cell functions including apoptosis. However, the signaling mechanism of SPH-induced apoptosis remains unclear. We have investigated whether SPH inhibits survival signaling in cells by inhibiting Akt kinase activity. This study demonstrates that treatment of Jurkat cells with SPH leads to Akt dephosphorylation as early as 15 min, and the cells undergo apoptosis after 6 h. This Akt dephosphorylation is not mediated through deactivation of upstream kinases, since SPH does not inhibit the upstream phosphoinositide-dependent kinase 1 (PDK1) phosphorylation. Rather, sensitivity to the Ser/Thr protein phosphatase inhibitors (calyculin A, phosphatidic acid, tautomycin, and okadaic acid) indicates an important role for protein phosphatase 1 (PP1) in this process. In vitro phosphatase assay, using Akt immunoprecipitate following treatment with SPH, reveals an increase in Akt-PP1 association as determined by immunoprecipitation analysis. Moreover, SPH-induced dephosphorylation of Akt at Ser(473) subsequently leads to the activation of GSK-3ß, caspase 3, PARP cleavage, and ultimately apoptosis. Pre-treatment with caspase 3 inhibitor z-VAD-fmk and Ser/Thr phosphatase inhibitor abrogates the effect of SPH on facilitating apoptosis. Altogether, these results demonstrate that PP1-mediated inhibition of the key anti-apoptotic protein, Akt, plays an important role in SPH-mediated apoptosis in Jurkat cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Proteína Fosfatasa 1/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Esfingosina/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Western Blotting , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Inmunoprecipitación , Células Jurkat , Toxinas Marinas , Ácido Ocadaico/farmacología , Oxazoles/farmacología , Fosforilación/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Unión Proteica/efectos de los fármacos , Proteína Fosfatasa 1/antagonistas & inhibidores , Piranos/farmacología , Serina/metabolismo , Compuestos de Espiro/farmacologíaRESUMEN
Glutathione (GSH) is the most abundant non-protein antioxidant in mammalian cells. It has been implicated in playing an important role in different signal transduction pathways, and its depletion is an early hallmark in the progression of apoptosis in response to a number of proapoptotic stimuli. We have selectively investigated the role of GSH in cytotoxic response of Jurkat and Molt-4 human leukemic cells to the anti-cancer drug Doxorubicin. In this study, we have shown that extracellular supplementation of GSH to human leukemic cells renders them a resistant phenotype to Doxorubicin treatment. Glutathione pre-treatment inhibits Doxorubicin-induced p53Ser(15) phosphorylation, caspase dependent ceramide (Cer) generation, Poly (ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation. Taken together, these results indicate that the major cellular antioxidant GSH influences the chemotherapeutic efficacy of Doxorubicin towards human leukemic cells.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Ceramidas/biosíntesis , Doxorrubicina/farmacología , Glutatión/fisiología , Leucemia/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Glutatión/farmacología , Humanos , Células Jurkat , FosforilaciónRESUMEN
Date seeds are a by-product of the date fruit processing industry with minimal human use; however, they are a rich source of polyphenols with a range of potential biological properties. The current study investigates the cytotoxicity of date seed polyphenols against cancer cell lines, its ability to combat hyperglycemia, its antioxidant potential and its anti-adipogenic effect. The present work aimed to establish the usefulness of date seeds in the food industry as a functional ingredient. The anti-tumour activity of DSE was tested in a panel of cell lines such as MCF-7, MDA-MB-231, Hep-G2, Caco-2, and PC-3 by measuring cell viability and cleaved PARP. Lipid accumulation and effect on the differentiation of 3T3-L1 cells (adipocytes) were tested with date seed extract treatments. The influence of date seed polyphenols on glucose uptake was studied in 3T3-L1 cells and C2C12 cells (muscle cells). The antioxidant activity of the polyphenols from date seed products such as date seed extract (DSE), date seed powder (DSP), and date seeds fortified bread (DSB) was tested following in-vitro digestion to study their stability in the gastrointestinal milieu. DSE treatment resulted in significantly reduced viability in MCF-7 and Hep-G2 cells with 48-h treatments. Glucose uptake increased in the adipocytes with DSE treatments; moreover, it inhibited adipocyte differentiation and lipid accumulation. DSE decreased the expression levels of PPAR-γ, C/EBPα, adiponectin and upregulated GLUT-4, and phospho-AMPK. This study also found that date seed samples retained antioxidant activity in the digestive milieu and concludes that the date seed polyphenols remain active in the digestive milieu and exhibit potential anti-hyperglycemic and anti-adipogenic activity.
RESUMEN
Curcumin has been shown to induce apoptosis in various malignant cancer cell lines. One mechanism of curcumin-induced apoptosis is through the PI3K/Akt signaling pathway. Akt, also known as protein kinase B (PKB), is a member of the family of phosphatidylinositol 3-OH-kinase regulated Ser/Thr kinases. The active Akt regulates cell survival and proliferation; and inhibits apoptosis. In this study we found that curcumin induces apoptotic cell death in MCF-7 cells, as assessed by MTT assay, DNA ladder formation, PARP cleavage, p53 and Bax induction. At apoptotic inducing concentration, curcumin induces a dramatic Akt phosphorylation, accompanied by an increased phosphorylation of glycogen synthase kinase 3beta (GSK3beta), which has been considered to be a pro-growth signaling molecule. Combining curcumin with PI3K inhibitor, LY290042, synergizes the apoptotic effect of curcumin. The inhibitor LY290042 was capable of attenuating curcumin-induced Akt phosphorylation and activation of GSK3beta. All together, our data suggest that blocking the PI3K/Akt survival pathway sensitizes the curcumin-induced apoptosis in MCF-7 cells.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis , Cromonas/farmacología , Curcumina/farmacología , Morfolinas/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Fosforilación/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Type 2 diabetes mellitus is increasing worldwide, and the United Arab Emirates is presenting one of the world's highest prevalence rates. Dietary polyphenols exert an antidiabetic effect by modulating carbohydrates digestion and cellular glucose uptake. Due to their particularly high content in polyphenols, date seeds represent a potential antidiabetic agent. This study aims to determine if date seed polyphenols inhibit the activity of the enzymes (α-amylase and α-glucosidase), responsible for the digestion of carbohydrates and modulating the glucose uptake by human liver cells. In vitro activity of the intestinal α-glucosidase, pancreatic α-amylase, the glucose uptake by HepG2 cells, and the expression of GLUT4 and AMPK analyzed by western blotting (with and without date seeds extract). Our result showed that the maximum enzymes inhibition was obtained with 400 µg/mL and 900 µg/mL DSE for α-amylase and α-glucosidase, respectively. The HepG2 cell viability significantly decreased up to 80% at 4000 µg/mL DSE. The expression of GLUT4 was higher at 100 µg/mL DSE (with insulin and without insulin). However, the expressions of P-AMPK and AMPK were increased by DSE, mainly in a non-insulin-dependent manner. Therefore, DSE, by inhibiting carbohydrate digestion and stimulating glucose uptake by HepG2, can potentially demonstrate the therapeutic potential for diabetes management.
RESUMEN
This study aimed to investigate the physicochemical properties, health-promoting benefits and rheological properties of an EPS produced by a novel probiotic Pediococcus pentosaceus M41 isolated from a marine source. P. pentosaceus M41 was able to produce an EPS with average molecular weight of 682.07â¯kDa. EPS-M41 consisted of arabinose, mannose, glucose and galactose with a molar ratio of 1.2:1.8:15.1:1.0. EPS-M41 structure could be proposed as â3)α-D-Glc(1â2)ß-D-Man(1â2)α-D-Glc(1â6)α-D-Glc(1â4)α-D-Glc(1â4)α-D-Gal(1â with arabinose linked at the terminals. At concentration of 10â¯mg.ml-1, the antioxidant capacity was 76.5% and 48.9% for DPPH and ABTS, respectively. EPS-M41 inhibited 86.8% and 90.8% of the α-amylase and α-glucosidase activities, respectively, at 100⯵g.ml-1. A 77.5% and 46.4% of antitumor inhibition occurred by EPS-M41 against Caco-2 and MCF-7 cells, respectively. The apparent viscosity (Æ) of all EPS-M41 solutions decreased with shear rate increases. Salt type and pH value had an impact on the rheological properties of EPS-M41.
Asunto(s)
Pediococcus pentosaceus/química , Polisacáridos Bacterianos/farmacología , Probióticos/química , Secuencia de Carbohidratos , Línea Celular Tumoral , Humanos , Peso Molecular , Polisacáridos Bacterianos/química , Reología , Sustancias Viscoelásticas/química , Sustancias Viscoelásticas/farmacología , ViscosidadRESUMEN
The polyphenolic content in date seeds, a promising functional ingredient for food, was characterised in three forms viz., date seed powder (DSP), date seed pita bread (DSB) and date seed extract (DSE). Bioaccessibility of the polyphenols from the samples was assessed by in-vitro digestion coupled with transport using Caco-2 cells. HPLC-ESI-UV/MS/MS-(IT) analysis recorded the presence of phenolic acids, flavanols, flavonols and flavones. Flavan-3-ols was the most significant group with the highest concentration in DSP, 47.91 ± 0.13 g/kg, after depolymerisation. Phenolic acids such as protocatechuic acid, vanillic acid and caffeoylshikimic acid were recovered from DSP and DSE after in-vitro digestion. In comparison, the recovery was significantly lower in the bread sample. Similarly, transport of protocatechuic acid, p-hydroxybenzoic acid, caffeoylshikimic acid, p-coumaric acid, syringic acid hexoside and diosmin through Caco-2 monolayer was observed in DSP and DSE, while protocatechuic acid and p-hydroxybenzoic acid were the only polyphenols transported from digested DSB.