RESUMEN
We present the purification and characterization of the two most abundant isoforms of lectins isolated from Tepary bean (Phaseolus acutifolius) seeds, which have been shown to differentially affect the survival of different cancer cells. They were separated by concanavalin A-affinity chromatography. After purification, to release the N-glycans, they were digested with the endoglycosidases PNGase and Glycanase A. Fractions resulted from the hydrolysis products were analyzed to determine their carbohydrate composition. Mass spectrometry data indicated that both isoforms contained high mannose glycans being mannose 6 the most abundant form. Furthermore, based on sequence Ans-X-Ser/Thr, where X is any amino acid except proline, a glycosylation site was determined on asparagine 36. When their metal requirement to preserve their biological activity was determined, the lectins showed differences. While lectin A (LA) agglutination activity was best in the presence of magnesium, lectin B (LB) was best with calcium. Additionally, only LA exhibited affinity to human type-A erythrocytes. Although both lectins showed small differences in their properties, an identical structure-model for both lectins was generated by the homology modelling process. Also, the analysis of ligand binding sites and in silico glycosylation were achieved. Molecular docking with colon adenocarcinoma associated-N-glycans revealed some highly possible interactions and, on the other hand, that N-glycan interaction zones of Tepary bean lectins is not restricted to the carbohydrate binding domain but to an extended part of their surface, which could lead new strategies to explain their biological activity.
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Adenocarcinoma , Neoplasias del Colon , Phaseolus , Humanos , Lectinas/química , Phaseolus/química , Phaseolus/metabolismo , Simulación del Acoplamiento Molecular , Manosa , Polisacáridos , Lectinas de Plantas/metabolismoRESUMEN
The potential of CdS quantum dots for biomedical and bioimaging applications depends on their cytotoxicity, which can be modulated by coating molecules. Using sulfur as a precursor can be used along with cadmium nitrate to synthesize CdS quantum dots with the fungus Fusarium oxysporum f. sp. lycopersici. The latter replaces pure chemical sulfur as a precursor for CdS quantum dot synthesis, thus transforming waste into a value-added product, increasing sustainability, reducing the environmental impact of the process through the implementation of green synthesis techniques, and contributing to the circular economy. Therefore, we compared the cytotoxicity on HT-29 cells of biogenic, and chemical CdSQDs, synthesized by a chemical method using pure sulfur. Biogenic and chemical CdSQDs had diameters of 4.08 ± 0.07 nm and 3.2 ± 0.20 nm, Cd/S molar ratio of 43.1 and 1.1, Z-potential of - 14.77 ± 0.64 mV and - 5.52 ± 1.11 mV, and hydrodynamic diameters of 193.94 ± 3.71 nm and 152.23 ± 2.31 nm, respectively. The cell viability improved 1.61 times for biogenic CdSQDs over chemical CdSQDs, while cytotoxicity, measured as IC50, diminished 1.88-times. The lower cytotoxicity of biogenic CdSQDs was attributed to their organic coating consisting of lipids, amino acids, proteins, and nitrate groups that interacted with CdS through -OH and -SH groups. Therefore, the biogenic synthesis of CdSQDs has repurposed a pathogenic fungus, taking advantage of the biomolecules it secretes, to transform hazardous sulfur waste and metal ions into stable CdSQDs with advantageous structural and cytotoxic properties for their potential application in biomedicine and bioimaging.
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Fusarium , Puntos Cuánticos , Puntos Cuánticos/toxicidad , Puntos Cuánticos/química , Hongos , AzufreRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM), a type of diabetes that occurs for the first time during pregnancy, may predispose the development of chronic degenerative diseases and metabolic alterations in mother and offspring. DNA methylation and microRNA (miRNA) expression are regulatory mechanisms of gene expression that may contribute to the pathogenesis of GDM. Therefore, we determined global DNA methylation and miR-126-3p expression levels in 8 and 7 Mexican women with and without GDM, respectively. METHODS AND RESULTS: Global DNA methylation was assessed by measuring the percentage of 5-methylcytosine (5-mC) in placenta, umbilical cord, and plasma DNA samples, whereas miR-126-3p expression was quantified by real-time PCR using the 2-ΔCt method of the corresponding RNA samples. A significant increase in the percentage of 5-mC was detected in placenta samples from GDM patients compared to healthy women, while plasma samples showed a significant decrease. Conversely, miR-126-3p expression levels were significantly higher in plasma from the GDM group, while placenta and umbilical cord samples showed no significant differences across experimental groups. Furthermore, DNA methylation correlated significantly with glucose levels in placenta and plasma. Likewise, miR-126-3p expression correlated significantly with plasma glucose, in addition to maternal body mass index (BMI at first trimester). CONCLUSION: The results indicate that GDM is associated with alterations in global DNA methylation levels and miR-126-3p expression in placenta and/or plasma, providing insights into future novel approaches to diagnose and/or prevent this pathology.
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Diabetes Gestacional , MicroARNs , Embarazo , Humanos , Femenino , Diabetes Gestacional/genética , Metilación de ADN/genética , Proyectos Piloto , Placenta/metabolismo , MicroARNs/metabolismoRESUMEN
High-fat/high-fructose diets promote early metabolic disorders in weight and lipid and glucose metabolism. Bioactive compounds such as polyphenols and fiber present in plant-based food prevent the development of metabolic disorders. The objective of the present study was to evaluate the effect of Phaseolus vulgaris L. Flor de Mayo Eugenia (FME) bean leaves on early metabolic alterations in male Wistar rats fed a high-fat/high-fructose diet. After proximate and chemical analysis of FME bean leaves, thirty-six male Wistar rats (ethical approval 06FCN2019 and 77FCN2019) were randomly assigned to one of four groups: 1) standard diet (S) fed with Rodent Laboratory Chow 5001®; 2) standard diet + 10% dry FME bean leaves (SBL); 3) high-fat (lard) and high-fructose diet (H); and 4) high-fat/high-fructose diet + 10% dry FME bean leaves (HBL). The study was carried out for six weeks. Group H exhibited early metabolic alterations compared to Group S: final weight gain (↑15%), abdominal fat accumulation (waist circumference, ↑11%), triglycerides (↑30%), glucose (↑16%), insulin resistance (HOMA-IR, ↑32%), and fecal triglycerides (↑284%) and decreased total short-chain fatty acids (SCFAs, ↓17%). FME bean leave supplementation (HBL) prevented body weight gain (↓12%), abdominal fat accumulation (waist circumference, ↓10%), and early insulin resistance (glucose area under the curve, ↓6%) compared to Group H. The supplementary bean leave diet increased SCFA production (↑54%), most likely mediated by the fiber and polyphenols present in the leaves. Therefore, bean leaves are a low-cost alternative for human nutritional care and prevention of early metabolic alterations.
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Resistencia a la Insulina , Enfermedades Metabólicas , Phaseolus , Animales , Dieta Alta en Grasa/efectos adversos , Fibras de la Dieta , Ácidos Grasos Volátiles/metabolismo , Fructosa/efectos adversos , Glucosa , Humanos , Insulina , Hojas de la Planta/metabolismo , Polifenoles/farmacología , Ratas , Ratas Wistar , Triglicéridos , Aumento de PesoRESUMEN
Tepary bean (Phaseolus acutifolius) lectins exhibit differential in vitro and in vivo biological effects, but their gastrointestinal interactions and digestion have not yet been assessed. This work aimed to evaluate the changes of a recombinant Tepary bean lectin (rTBL-1) through an in vitro and ex vivo gastrointestinal process. A polyclonal antibody was developed to selectively detect rTBL-1 by Western blot (WB) and immunohistochemical analysis. Everted gut sac viability was confirmed until 60 min, where protein bioaccessibility, apparent permeability coefficient, and efflux ratio showed rTBL-1 partial digestion and absorption. Immunoblot assays suggested rTBL-1 internalization, since the lectin was detected in the digestible fraction. The immunohistochemical assay detected rTBL-1 presence at the apical side of the small intestine, potentially due to the interaction with the intestinal cell membrane. The in silico interactions between rTBL-1 and some saccharides or derivatives showed high binding affinity to sialic acid (-6.70 kcal/mol) and N-acetylglucosamine (-6.10 kcal/mol). The ultra-high-performance liquid chromatography-electron spray ionization-quantitative time-of-flight coupled to mass spectrometry (UHPLC-ESI-QTOF/MS) analysis showed rTBL-1 presence in the gastric content and the non-digestible fraction after intestinal simulation conditions. The results indicated that rTBL-1 partially resisted the digestive conditions and interacted with the intestinal membrane, whereas its digestion allowed the absorption or internalization of the protein or the derivative peptides. Further purification of digestion samples should be conducted to identify intact rTBL-1 protein and digested peptides to assess their physiological effects.
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Permeabilidad de la Membrana Celular , Absorción Intestinal , Mucosa Intestinal/metabolismo , Lectinas/metabolismo , Phaseolus/genética , Proteínas Recombinantes/metabolismo , Metabolismo de los Hidratos de Carbono , Carbohidratos/química , Permeabilidad de la Membrana Celular/efectos de los fármacos , Supervivencia Celular , Cromatografía Líquida de Alta Presión , Inmunohistoquímica , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Lectinas/química , Lectinas/genética , Ligandos , Modelos Moleculares , Unión Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacología , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Relación Estructura-ActividadRESUMEN
Angiogenesis, the formation of new blood vessels, underlies tissue development and repair. Some medicinal plant-derived compounds can modulate the angiogenic response. Heliopsis longipes, a Mexican medicinal plant, is widely used because of its effects on pain and inflammation. The main bioactive phytochemicals from H. longipes roots are alkamides, where affinin is the most abundant. Scientific studies show various medical effects of organic extracts of H. longipes roots and affinin that share some molecular pathways with the angiogenesis process, with the vasodilation mechanism of action being the most recent. This study investigates whether pure affinin and the ethanolic extract from Heliopsis longipes roots (HLEE) promote angiogenesis. Using the aortic ring rat assay (ex vivo method) and the direct in vivo angiogenesis assay, where angioreactors were implanted in CD1 female mice, showed that affinin and the HLEE increased vascular growth in a dose-dependent manner in both bioassays. This is the first study showing the proangiogenic effect of H. longipes. Further studies should focus on the mechanism of action and its possible therapeutic use in diseases characterized by insufficient angiogenesis.
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Asteraceae/química , Etanol/química , Neovascularización Fisiológica/efectos de los fármacos , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Alcamidas Poliinsaturadas/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Plantas Medicinales , Alcamidas Poliinsaturadas/química , Alcamidas Poliinsaturadas/aislamiento & purificación , RatasRESUMEN
AIM: To determine whether rs1805086 is associated with obesity and metabolic disturbances in a Mexican adult population. SUBJECTS AND METHODS: We genotyped rs1805086 in 1024 men and women aged 18-58 years. Anthropometric and body fat data were used to estimate obesity. Biochemical parameters were measured and DNA was used to determine the rs1805086 genotype. RESULTS: rs1805086 heterozygous AG frequency was 5.4%, and the homozygous for the risk allele GG was absent. Heterozygous had higher levels of body mass index (BMI) and waist/height ratio (WHtR). Heterozygous subjects showed a greater total and central obesity compared to the homozygous for ancestral allele AA (OR BMI > 30 kg/m2 = 2.35, 95% CI 1.29-4.29; OR WHtR > 0.5 = 2.03, 95% CI 1.19-3.45; OR elevated fat mass (EFM) %= 1.72, 95% CI 1.01-2.92; OR fat mass index (FMI)>p85 = 1.96, 95% CI 1.05-3.68). rs1805086 was not associated with metabolic alterations. CONCLUSION: Heterozygosity for rs1805086 showed a predisposition to having elevated overall and central obesity parameters. This association with adiposity seems to be independent of metabolic risk.
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Miostatina/genética , Obesidad/genética , Tejido Adiposo/metabolismo , Adolescente , Adulto , Índice de Masa Corporal , Femenino , Genotipo , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/patología , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
Muscle growth is regulated by several factors including the growth differentiation factor 8, known as myostatin, an inhibitor of myocyte differentiation and proliferation. Research on myostatin regulation was already conducted to improve growth rates in farmed animals, including aquatic species. To explore the effects of myostatin inactivation in a commercial marine fish (spotted rose snapper, Lutjanus guttatus) in vivo, we induced post-transcriptional silencing (knockdown) of myostatin-1 (mstn-1) by injecting dsiRNA directly into the muscle of juvenile fish (87 days post-hatch) using a commercial polymer as vehicle. Results show a significant decrease in mstn-1 expression starting at 2 days after injection and for up to 5 days. Knockdown of mstn-1 caused muscle fiber hypertrophy (but not hyperplasia); however, there were no significant changes in weight or length. Although still experimental, this study provides evidence that temporary knockdown of mstn-1 in a commercial marine fish in vivo promotes fiber hypertrophy and therefore could potentially help grow-out programmes in fish aquaculture.
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Hipertrofia/genética , Miostatina/genética , Miostatina/metabolismo , Animales , Acuicultura , Peces/genética , Hiperplasia/genética , Músculo Esquelético/metabolismo , Perciformes/genética , Interferencia de ARN/fisiologíaRESUMEN
Although cognitive impairment (CI) is classically associated with aging, it has been proposed that neurological pathologies may increase the risk to suffer CI. Despite the evidence of an elevated prevalence of CI in patients with multiple sclerosis (MS), it is not considered among standard clinical evaluations, due the lack of specialists and time required. The aim of this study was to evaluate if lipid profile is associated with cognitive performance in persons with MS. Twenty patients with MS were evaluated. Montreal Cognitive Assessment (MoCA) was employed to determine cognitive performance. CI was observed in 85% of patients, with memory recall and language as the most affected domains. Despite biomarkers were mostly found within reference values, several correlations were observed. MoCA total score was correlated with cholesterol (r = - 0.468, p = 0.037) and LDL (r = - 0.453, p = 0.045). Visuospatial domain was correlated with LDL (r = - 0.493, p = 0.027). Attention domain correlated with triglycerides (r = - 0.455, p = 0.044) and cholesterol (r = - 0.549, p = 0.012). When the person reaches borderline levels of triglycerides, LDL and cholesterol a decrease in cognitive performance can be observed. The mechanism underlying this association has not been established still, it has been proposed that it could be linked with neuroinflammation, alterations in synapses and in the metabolism of amyloid-ß protein. This study settles the potential importance that lipid profile could have on cognitive performance in MS. Further studies are needed to establish optimal levels and implication of lipid profile in the diagnosis and monitoring of cognitive performance in Mexican people with MS.
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HDL-Colesterol/sangre , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Disfunción Cognitiva/sangre , Esclerosis Múltiple/sangre , Triglicéridos/sangre , Adulto , Biomarcadores/sangre , Cognición/fisiología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/fisiopatología , Femenino , Acetato de Glatiramer/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Interferones/uso terapéutico , Lipidómica/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/fisiopatologíaRESUMEN
A Tepary bean lectin fraction (TBLF) has been studied because it exhibits differential cytotoxic and anticancer effects on colon cancer. The present work focuses on the evaluation of the apoptotic mechanism of action on colon cancer cells. Initially, lethal concentrations (LC50) were obtained for the three studied cell lines (HT-29, RKO and SW-480). HT-29 showed the highest LC50, 10 and 100 times higher than that of RKO and SW-480 cells, respectively. Apoptosis was evaluated by flow cytometry, where HT-29 cells showed the highest levels of early and total apoptosis, caspases activity was confirmed and necrosis was discarded. The effect on cell cycle arrest was shown in the G0/G1 phase. Specific apoptosis-related gene expression was determined, where an increase in p53 and a decrease in Bcl-2 were observed. Expression of p53 gene showed the maximum level at 8 h with an important decrease at 12 and 24 h, also the phosphorylated p53(ser46) increased at 8 h. Our results show that TBLF induces apoptosis in colon cancer cells by p-p53(ser46) involvement. Further studies will focus on studying the specific signal transduction pathway.
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Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Lectinas/farmacología , Phaseolus/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HT29 , Humanos , Lectinas/química , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Lectins are bioactive proteins with the ability to recognize cell membrane carbohydrates in a specific way. Diverse plant lectins have shown diagnostic and therapeutic potential against cancer, and their cytotoxicity against transformed cells is mediated through the induction of apoptosis. Previous works have determined the cytotoxic activity of a Tepary bean (Phaseolus acutifolius) lectin fraction (TBLF) and its anti-tumorigenic effect on colon cancer. In this work, lectins from the TBLF were additionally purified by ionic-exchange chromatography. Two peaks with agglutination activity were obtained: one of them was named TBL-IE2 and showed a single protein band in two-dimensional electrophoresis; this one was thus selected for coupling to quantum dot (QD) nanoparticles by microfluidics (TBL-IE2-QD). The microfluidic method led to low sample usage, and resulted in homogeneous complexes, whose visualization was achieved using multiphoton and transmission electron microscopy. The average particle size (380 nm) and the average zeta potential (-18.51 mV) were determined. The cytotoxicity of the TBL-IE2 and TBL-IE2-QD was assayed on HT-29 colon cancer cells, showing no differences between them (p ≤ 0.05), where the LC50 values were 1.0 × 10-3 and 1.7 × 10-3 mg/mL, respectively. The microfluidic technique allowed control of the coupling between the QD and the protein, substantially improving the labelling process, providing a rapid and efficient method that enabled the traceability of lectins. Future studies will focus on the potential use of the QD-labelled lectin to recognize tumor tissues.
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Microfluídica , Phaseolus/metabolismo , Lectinas de Plantas/metabolismo , Puntos Cuánticos/metabolismo , Coloración y Etiquetado , Muerte Celular/efectos de los fármacos , Fluorescencia , Células HT29 , Humanos , Lectinas de Plantas/aislamiento & purificación , Lectinas de Plantas/farmacologíaRESUMEN
Snakebite envenoming is a serious medical problem in different areas of the world. In Latin America, the major prevalence is due to snakes of the family Viperidae, where rattlesnakes (Crotalus) are included. They produce hemotoxic venom which causes bleeding, tissue degradation and necrosis. Each venom has several enzymatic activities, producing different effects in the envenoming, doing its clinical effects difficult to study. Comparison between venom molecules is also difficult when different techniques are used, and therefore, their identification/characterization using the same methodology is necessary. In this work, a general biochemical characterization in snake venom of serine proteases (SVSP), phospholipases A2 (PLA2), metalloproteases (SVMP) and hyaluronidases (SVH) of Crotalus aquilus (Ca), Crotalus polystictus (Cp) and Crotalus molossus nigrescens (Cmn) was done. Differences in protein pattern, enzyme content and enzymatic activities were observed. All the venoms showed high PLA2 activity, high molecular weight SVSP, and a wide variety of SVMP and SVH forms. Ca and Cp showed the highest enzymatic activities of SVMP and SVSP trypsin-like and chymotrypsin-like, whereas Cmn showed the highest SVH and similar PLA2 activity with Ca. All the venoms showed peptides with similar molecular weight to crotamine-like myotoxins. No previous biochemical characterization of C. aquilus has been reported and there are no previous analyses that include these four protein families in these Crotalus venoms.
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Hidrolasas/metabolismo , Hidrolasas/toxicidad , Venenos de Serpiente/enzimología , Animales , Crotalus , Metaloproteasas/análisis , México , Serina Proteasas/análisis , Especificidad de la EspecieRESUMEN
Lectins are proteins that have the ability to recognize and bind in a reversible and specific way to free carbohydrates or glycoconjugates of cell membranes. For these reasons, they have been extensively used in a wide range of industrial and pharmacological applications. Currently, there is great interest in their production on a large scale. Unfortunately, conventional techniques do not provide the appropriate platform for this purpose and therefore, the heterologous production of lectins in different organisms has become the preferred method in many cases. Such systems have the advantage of providing better yields as well as more homogeneous and better-defined properties for the resultant products. However, an inappropriate choice of the expression system can cause important structural alterations that have repercussions on their biological activity since the specificity may lay in their post-translational processing, which depends largely on the producing organism. The present review aims to examine the most representative studies in the area, exposing the four most frequently used systems (bacteria, yeasts, plants and animal cells), with the intention of providing the necessary information to determine the strategy to follow in each case as well as their respective advantages and disadvantages.
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Expresión Génica , Lectinas/metabolismo , Animales , Carbohidratos/química , Lectinas/clasificación , Lectinas/aislamiento & purificación , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Levaduras/metabolismoRESUMEN
Digestive system cancers-those of the esophagus, stomach, small intestine, colon-rectum, liver, and pancreas-are highly related to genetics and lifestyle. Most are considered highly mortal due to the frequency of late diagnosis, usually in advanced stages, caused by the absence of symptoms or masked by other pathologies. Different tools are being investigated in the search of a more precise diagnosis and treatment. Plant lectins have been studied because of their ability to recognize and bind to carbohydrates, exerting a variety of biological activities on animal cells, including anticancer activities. The present report integrates existing information on the activity of plant lectins on various types of digestive system cancers, and surveys the current state of research into their properties for diagnosis and selective treatment.
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Neoplasias del Sistema Digestivo/tratamiento farmacológico , Lectinas de Plantas/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Tecnología Biomédica , HumanosRESUMEN
Heliopsis longipes roots have been widely used in Mexican traditional medicine to relieve pain, mainly, toothaches. Previous studies have shown that affinin, the major alkamide of these roots, induces potent antinociceptive and anti-inflammatory activities. However, the effect of H. longipes root extracts and affinin on the cardiovascular system have not been investigated so far. In the present study, we demonstrated that the dichloromethane and ethanolic extracts of H. longipes roots, and affinin, isolated from these roots, produce a concentration-dependent vasodilation of rat aorta. Affinin-induced vasorelaxation was partly dependent on the presence of endothelium and was significantly blocked in the presence of inhibitors of NO, H2S, and CO synthesis (NG-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (PAG), and chromium mesoporphyrin (CrMP), respectively); K⺠channel blockers (glibenclamide (Gli) and tetraethyl ammonium (TEA)), and guanylate cyclase and cyclooxygenase inhibitors (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and indomethacin (INDO), respectively). Our results demonstrate, for the first time, that affinin induces vasodilation by mechanisms that involve gasotransmitters, and prostacyclin signaling pathways. These findings indicate that this natural alkamide has therapeutic potential in the treatment of cardiovascular diseases.
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Amidas/aislamiento & purificación , Amidas/farmacología , Asteraceae/química , Epoprostenol/metabolismo , Gasotransmisores/metabolismo , Transducción de Señal/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Amidas/química , Animales , Aorta/efectos de los fármacos , Aorta/fisiología , AMP Cíclico/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Indometacina/farmacología , Masculino , Cloruro de Metileno , Modelos Biológicos , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Alcamidas Poliinsaturadas , Canales de Potasio/metabolismo , Ratas WistarRESUMEN
Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain and a decrease in food intake when using a dose of 50 mg/kg on alternate days for six weeks. Taking this information into account, the focus of this work was to evaluate the effect of the TBLF on colon cancer using 1,2-dimethylhydrazine (DMH) or azoxy-methane/dextran sodium sulfate (AOM/DSS) as colon cancer inductors. Rats were treated with DMH or AOM/DSS and then administered with TBFL (50 mg/kg) for six weeks. TBLF significantly decreased early tumorigenesis triggered by DMH by 70%, but without any evidence of an apoptotic effect. In an independent experiment, AOM/DSS was used to generate aberrant cryptic foci, which decreased by 50% after TBLF treatment. TBLF exhibited antiproliferative and proapoptotic effects related to a decrease of the signal transduction pathway protein Akt in its activated form and an increase of caspase 3 activity, but not to p53 activation. Further studies will deepen our knowledge of specific apoptosis pathways and cellular stress processes such as oxidative damage.
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Antineoplásicos Fitogénicos/farmacología , Neoplasias del Colon/tratamiento farmacológico , Phaseolus/química , Lectinas de Plantas/farmacología , Células 3T3 , Animales , Antineoplásicos Fitogénicos/química , Apoptosis , Caspasa 3/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Lectinas de Plantas/química , Ratas Sprague-Dawley , Semillas/química , Transducción de SeñalRESUMEN
Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models.
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Resistencia a la Insulina , Isoleucina/análogos & derivados , Obesidad/tratamiento farmacológico , Trigonella/química , Animales , Glucosa/metabolismo , Humanos , Técnicas In Vitro , Isoleucina/farmacología , Isoleucina/uso terapéutico , Hígado/efectos de los fármacos , Hígado/fisiopatología , Pruebas de Función Hepática , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Obesidad/metabolismo , Obesidad/fisiopatología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Recent findings made by our group indicate that the iron content in Phaseolus vulgaris leaves is at least four times greater than in grains therefore, we evaluated the effect of supplementation with bean leaf (iron content of 275 mg/kg on a dry basis) in iron-deficient rats. Anemia was induced by feeding rats with an iron-deficient diet (IDD) for 11 days and iron-recovery diets were subsequently tested for 14 days using a normal diet, a 10 % bean leaf-supplemented IDD (BLSD) or a ferrous sulfate-supplemented IDD. Decreased levels of leukocytes (64 %), erythrocytes (30 %), lymphocytes (62 %), granulocytes (72 %), hematocrit (34 %), hemoglobin (35 %), and ferritin (34 %) were observed in the iron-deficient rats compared to the control rats. BLSD supplementation showed the highest recovery values relative to those recorded for control rats: leukocytes (40 %), erythrocytes (24 %), lymphocytes (33 %), granulocytes (88 %), hematocrit (17 %), and hemoglobin (18 %), suggesting that common bean leaves could be a good source of bioavailable iron with possible immunomodulatory effects.
Asunto(s)
Hierro de la Dieta/análisis , Phaseolus/química , Hojas de la Planta/química , Anemia Ferropénica/sangre , Anemia Ferropénica/prevención & control , Animales , Biomarcadores/sangre , Suplementos Dietéticos , Modelos Animales de Enfermedad , Eritrocitos/metabolismo , Femenino , Ferritinas/sangre , Ferritinas/deficiencia , Compuestos Ferrosos/administración & dosificación , Granulocitos/metabolismo , Hematócrito , Hemoglobinas/deficiencia , Hemoglobinas/metabolismo , Hierro de la Dieta/administración & dosificación , Leucocitos/metabolismo , Linfocitos/metabolismo , Ratas , Ratas WistarRESUMEN
This study investigated the effect of a ß-x200B;hydroxyphosphonate analog of Ê-carnitine (L-CA) (CAS number: 1220955-x200B;20-3, Component: 1221068-91-2, C12H29NO4PI), (3-Hexanaminium, 1-(dimethoxyphosphinyl)-2-hydroxy-N,N,N,5-x200B;tetramethy-iodide (1:1), (2R, 3S)) on parameters related with type-2 diabetes in an in vitro model. Nontoxic concentrations of L-CA were assayed and compared to commercial Ê-carnitine effects. L-CA did not affect adipogenesis in normal cells, but an increment of TG accumulation was observed on insulin-resistant adipocytes (80%) when compared with resistant control. L-CA also stimulated glucose analog 2-NBDG uptakes on insulin-resistant adipocytes in a similar way as insulin when compared to insulin-resistant cells. Our results show that the L-CA promoted insulin-like responses on insulin-resistant adipocytes without appreciable pro-adipogenic effect in sensitive adipocytes.
Asunto(s)
Adipocitos/efectos de los fármacos , Carnitina/análogos & derivados , Carnitina/farmacología , Resistencia a la Insulina , Células 3T3-L1 , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hipoglucemiantes/farmacología , RatonesRESUMEN
Gestational diabetes mellitus (GDM) is a common metabolic disorder, usually diagnosed during the third trimester of pregnancy that usually disappears after delivery. In GDM, the excess of glucose, fatty acids, and amino acids results in foetuses large for gestational age. Hyperglycaemia and insulin resistance accelerate the metabolism, raising the oxygen demand, and creating chronic hypoxia and inflammation. Women who experienced GDM and their offspring are at risk of developing type-2 diabetes, obesity, and other metabolic or cardiovascular conditions later in life. Genetic factors may predispose the development of GDM; however, they do not account for all GDM cases; lifestyle and diet also play important roles in GDM development by modulating epigenetic signatures and the body's microbial composition; therefore, this is a condition with a complex, multifactorial aetiology. In this context, we revised published reports describing GDM-associated single-nucleotide polymorphisms (SNPs), DNA methylation and microRNA expression in different tissues (such as placenta, umbilical cord, adipose tissue, and peripheral blood), and microbial composition in the gut, oral cavity, and vagina from pregnant women with GDM, as well as the bacterial composition of the offspring. Altogether, these reports indicate that a number of SNPs are associated to GDM phenotypes and may predispose the development of the disease. However, extrinsic factors (lifestyle, nutrition) modulate, through epigenetic mechanisms, the risk of developing the disease, and some association exists between the microbial composition with GDM in an organ-specific manner. Genes, epigenetic signatures, and microbiota could be transferred to the offspring, increasing the possibility of developing chronic degenerative conditions through postnatal life.