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1.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 165-170, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817351

RESUMEN

In current study, Maize (Zea mays L.) husk leave extracts were appraised for biological activities such as cytotoxicity, antidiabetic, antioxidant and antimicrobial. Maceration was performed to collect various fractions of husk leave extracts using a pool of solvents i.e., n-hexane, chloroform, ethyl acetate, butanol and methanol. Antioxidant potential was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging, reducing power and linoleic acid oxidation assay, using butylated hydroxy toluene (BHT) as a positive control. Total phenolic and flavonoid contents were found to be 18.47-425.11 mg/100 g GAE and 5.83-16.72 mg/100 g CE, respectively. The DPPH scavenging assay was exhibited in the range of 76.36 to 88.53%. The percentage inhibition in linoleic acid oxidation was found from 10.16 to 79.51%. Significant antimicrobial activity was demonstrated by husk leaf extracts against bacterial strains and fungal strains using disc diffusion and minimum inhibitory concentration (MIC) method. Amylase alpha assay was employed to analyze the antidiabetic activity which ranged between 9.52-24.81%. Cytotoxicity was evaluated by % age lysis (0.35-9.54%), while thrombolytic activity ranged between 7.67 to 31.27%. The results presented in this study revealed that maize (Zea mays L.) husk leaf extracts can be a valuable source of biologically active compounds and may be consumed as a source of potent herbal medicine in pharmaceuticals.


Asunto(s)
Antioxidantes/farmacología , Hipoglucemiantes/farmacología , Hojas de la Planta/química , Zea mays/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antioxidantes/química , Aspergillus niger/efectos de los fármacos , Aspergillus niger/fisiología , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/fisiología , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Hemólisis/efectos de los fármacos , Humanos , Hipoglucemiantes/química , Pruebas de Sensibilidad Microbiana/métodos , Extractos Vegetales/química , Extractos Vegetales/farmacología
2.
Molecules ; 26(11)2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-34073461

RESUMEN

Uncaria tomentosa (Willd.) DC is a woody climber species originating from South and Central America that has been used in the therapy of asthma, rheumatism, hypertension, and blood purification. Our previous study showed that U. tomentosa extracts altered human erythrocyte shape, which could be due to incorporation of the compounds contained in extracts into the erythrocyte membrane. The aim of the present study was to determine how the compounds contained in U. tomentosa extracts incorporate into the human erythrocyte membrane. The study has assessed the effect of aqueous and ethanolic extracts from leaves and bark of U. tomentosa on the osmotic resistance of the human erythrocyte, the viscosity of erythrocyte interior, and the fluidity of erythrocyte plasma membrane. Human erythrocytes were incubated with the studied extracts in the concentrations of 100, 250, and 500 µg/mL for 2, 5, and 24 h. All extracts tested caused a decrease in erythrocyte membrane fluidity and increased erythrocyte osmotic sensitivity. The ethanolic extracts from the bark and leaves increased viscosity of the erythrocytes. The largest changes in the studied parameters were observed in the cells incubated with bark ethanolic extract. We consider that the compounds from U. tomentosa extracts mainly build into the outer, hydrophilic monolayer of the erythrocyte membrane, thus protecting the erythrocytes against the adverse effects of oxidative stress.


Asunto(s)
Uña de Gato/química , Membrana Eritrocítica/efectos de los fármacos , Eritrocitos/citología , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Relación Dosis-Respuesta a Droga , Etanol , Humanos , Espectroscopía de Resonancia Magnética , Fragilidad Osmótica , Estrés Oxidativo , Corteza de la Planta , Hojas de la Planta/química , Polifenoles , Viscosidad , Agua
3.
Eur J Med Chem ; 219: 113416, 2021 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-33887682

RESUMEN

Parasites of the Plasmodium genus are unable to produce purine nucleotides de novo and depend completely on the salvage pathway. This fact makes plasmodial hypoxanthine-guanine-(xanthine) phosphoribosyltransferase [HG(X)PRT] a valuable target for development of antimalarial agents. A series of nucleotide analogues was designed, synthesized and evaluated as potential inhibitors of Plasmodium falciparum HGXPRT, P. vivax HGPRT and human HGPRT. These novel nucleoside phosphonates have a pyrrolidine, piperidine or piperazine ring incorporated into the linker connecting the purine base to a phosphonate group(s) and exhibited a broad range of Ki values between 0.15 and 72 µM. The corresponding phosphoramidate prodrugs, able to cross cell membranes, have been synthesized and evaluated in a P. falciparum infected human erythrocyte assay. Of the eight prodrugs evaluated seven exhibited in vitro antimalarial activity with IC50 values within the range of 2.5-12.1 µM. The bis-phosphoramidate prodrug 13a with a mean (SD) IC50 of 2.5 ± 0.7 µM against the chloroquine-resistant P. falciparum W2 strain exhibited low cytotoxicity in the human hepatocellular liver carcinoma (HepG2) and normal human dermal fibroblasts (NHDF) cell lines at a concentration of 100 µM suggesting good selectivity for further structure-activity relationship investigations.


Asunto(s)
Antimaláricos/síntesis química , Inhibidores Enzimáticos/química , Nucleótidos/química , Pentosiltransferasa/antagonistas & inhibidores , Proteínas Protozoarias/antagonistas & inhibidores , Antimaláricos/metabolismo , Antimaláricos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Resistencia a Medicamentos/efectos de los fármacos , Inhibidores Enzimáticos/metabolismo , Eritrocitos/citología , Eritrocitos/metabolismo , Eritrocitos/parasitología , Humanos , Nucleótidos/metabolismo , Pentosiltransferasa/metabolismo , Piperazina/química , Piperidinas/química , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/enzimología , Plasmodium vivax/enzimología , Profármacos/síntesis química , Profármacos/química , Profármacos/metabolismo , Profármacos/farmacología , Proteínas Protozoarias/metabolismo , Pirrolidinas/química , Relación Estructura-Actividad
4.
Eur J Haematol ; 107(1): 3-23, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33715214

RESUMEN

Myelodysplastic syndromes (MDS) are a group of malignant hematologic diseases characterized by ineffective hematopoiesis, which may lead to chronic anemia and transfusion dependency, with up to 30% of patients progressing to acute myeloid leukemia (AML). Studies suggest transfusion dependency may impact overall survival (OS); however, there is a lack of evidence concerning the association between transfusion status (TS) and OS in patients with MDS who become transfusion independent (TI) after treatment. In addition, the holistic impact of TS on other clinical, economic, and humanistic outcomes has not been well understood. We conducted a systematic literature review (SLR) to understand this impact. Ten studies were included and showed consistent decrease in OS in transfusion dependent (TD) compared with TI patients. These findings were confirmed by a meta-analysis (MA) reporting better OS prognosis for TI patients. A second SLR was conducted to understand the association between TS and other clinical, economic, and humanistic outcomes. Twenty-eight studies were included and showed better prognosis for other outcomes, including AML progression and leukemia-free survival for TI patients. Risk of AML progression and cumulative non-leukemic death assessed by the MA showed a trend toward worse prognosis and higher risk of AML progression for TD patients. Lower healthcare resource utilization, better quality of life, and reduced non-leukemic death for TI patients were observed. Studies not eligible for MA also showed better clinical, economic, and humanistic outcomes for TI patients. These findings contribute to understanding the association between transfusion dependence and OS among other outcomes in patients with MDS.


Asunto(s)
Transfusión de Eritrocitos/métodos , Eritrocitos/citología , Leucemia Mieloide Aguda/complicaciones , Síndromes Mielodisplásicos/terapia , Anemia/complicaciones , Teorema de Bayes , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Método de Montecarlo , Síndromes Mielodisplásicos/complicaciones , Fenotipo , Pronóstico , Calidad de Vida , Riesgo , Resultado del Tratamiento
5.
Biochemistry ; 59(33): 3019-3025, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32794692

RESUMEN

Metal nanoparticles (AgNPs and ZnONPs) were synthesized using a green methodology with the green leaves extract of the Bedu (Ficus palmata) tree as a reducing agent and the support of natural fibers. The synthesized AgNPs and ZnONPs were characterized by several techniques, including ultraviolet-visible spectral analysis, powder X-ray diffraction crystal analysis, scanning electron microscopy, EDAX, transmission electron microscopy, and Fourier transform infrared spectroscopy, which confirmed that the synthesized particles are in the nano range (1-100 nm), i.e., 30 nm for AgNPs with polydispersity and a spherical shape, whereas the average size of synthesized ZnONPs is 34 nm and they seem to exhibit a distorted spherical shape. The results of thermogravimetric analysis confirmed a weight loss of 18.02% for AgNPs under exothermic conditions due to the desorption of water, and ZnONPs show weight loss between 265 and 500 °C. Both synthesized MNPs are highly thermally stable. Anti-inflammatory and anti-diabetic studies of metal NPs have been evaluated. The AgNPs and ZnONPs of F. palmata leaves showed remarkably highly potent activity for respective strains. In vitro anti-diabetic activity was found for inhibition of α-amylases and α-glucosidases by synthesized silver nanoparticles.


Asunto(s)
Antiinflamatorios , Ficus/química , Hipoglucemiantes , Nanopartículas del Metal/química , Extractos Vegetales , Hojas de la Planta/química , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Células Cultivadas , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Tecnología Química Verde/métodos , Humanos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Concentración 50 Inhibidora , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Plata/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Zinc/química , alfa-Amilasas/antagonistas & inhibidores , alfa-Glucosidasas/efectos de los fármacos , alfa-Glucosidasas/metabolismo
6.
Chembiochem ; 21(22): 3266-3272, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-32662172

RESUMEN

The elemental composition of a single yeast, green alga, or red blood cell (RBC) was precisely determined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in fast time-resolved analysis (TRA) mode. The technique is known as single-cell (SC)-ICP-MS. Phosphorus, sulfur, magnesium, zinc, and iron were detected in the three types of cell. The elemental composition of yeast and green alga obtained by SC-ICP-MS was consistent with results obtained from conventional ICP-MS measurements following acid digestion of the cells. Slight differences were found in the measured values between SC-ICP-MS and the conventional ICP-MS results for RBC. However, the SC-ICP-MS results for S and Fe in RBC were closer to the estimated values for these elements that were calculated from the level of hemoglobin in RBCs. The data suggest that SC-ICP-MS is suitable for the analysis of various cell types, namely, fungus, plant, and animal cells.


Asunto(s)
Hierro/análisis , Magnesio/análisis , Fósforo/análisis , Análisis de la Célula Individual , Azufre/análisis , Zinc/análisis , Animales , Células Cultivadas , Chlamydomonas reinhardtii/química , Chlamydomonas reinhardtii/citología , Eritrocitos/química , Eritrocitos/citología , Masculino , Espectrometría de Masas , Ratas , Ratas Wistar , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/citología , Factores de Tiempo
7.
Curr HIV Res ; 18(4): 237-247, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32386495

RESUMEN

BACKGROUND: Lipid-based formulations have been confirmed to lower some side effects of drugs and can be tailor-made to offer sustained drug release of drugs with short half-life like stavudine. AIM: This study aimed to evaluate the immunomodulatory properties of stavudine-loaded solid lipid microparticles (SLMs) using immunocompromised Wistar rats. METHODS: The SLMs were formulated by the homogenization method. The optimized batches were used for further in vivo studies. The effect of formulation on the CD4 count and the haematological properties of immunocompromised Wistar rats were studied. RESULTS: The particle size range was 4 -8 µm, EE range was 85-93 % and maximum drug release was observed at 10 h. The CD4 cells increased from 115 ± 3.17 cell/mm3 at day zero to 495 ± 5.64 cell/mm3 at day 14 of treatment and 538 ± 6.31 cell/mm3 at day 21. The red blood cells increased from 2.64 ± 1.58 (x 106/mm3) at day zero to 6.96 ± 3.47 (x 106/mm3) at day 14 and 7.85 ± 3.64 (x 106/mm3) at day 21. PCV increased significantly (p < 0.05) to about 42-50 % at day 21 in the groups that received the SLMs formulations. White blood cells (WBC) also were 12 x 103/mm3, for SLM formulations, while the rats that received plain stavudine exhibited WBC of 9.6 x 103/mm3 at day 21. The histopathological studies revealed that oral stavudine-loaded SLMs had no significant damage to the kidney, liver, spleen and the brain of Wistar rats. CONCLUSION: The formulations exhibited significantly higher immunomodulatory properties than plain stavudine (p<0.05) and showed good properties for once daily oral administration and could be a better alternative to plain stavudine tablets for the management of patients living with HIV.


Asunto(s)
Fármacos Anti-VIH/farmacocinética , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Huésped Inmunocomprometido , Leucocitos/efectos de los fármacos , Estavudina/farmacocinética , Administración Oral , Animales , Fármacos Anti-VIH/metabolismo , Fármacos Anti-VIH/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/inmunología , Preparaciones de Acción Retardada/administración & dosificación , Portadores de Fármacos/administración & dosificación , Composición de Medicamentos/métodos , Recuento de Eritrocitos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/inmunología , Femenino , Humanos , Riñón/efectos de los fármacos , Riñón/inmunología , Lecitinas/química , Recuento de Leucocitos , Leucocitos/citología , Leucocitos/inmunología , Hígado/efectos de los fármacos , Hígado/inmunología , Masculino , Aceite de Palma/química , Tamaño de la Partícula , Ratas , Ratas Wistar , Bazo/efectos de los fármacos , Bazo/inmunología , Estavudina/metabolismo , Estavudina/farmacología
8.
Sci Rep ; 10(1): 8602, 2020 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-32451387

RESUMEN

Anaemia therapy or perisurgical support of erythropoiesis often require both, EPO and iron medication. However, excessive iron medication can result in iron overload and it is challenging to control haemoglobin levels in a desired range. To support this task, we develop a biomathematical model to simulate EPO- and iron medication in humans. We combine our previously established model of human erythropoiesis including comprehensive pharmacokinetic models of EPO applications with a newly developed model of iron metabolism including iron supplementation. Equations were derived by translating known biological mechanisms into ordinary differential equations. Qualitative model behaviour is studied in detail considering a variety of interventions such as bleeding, iron malnutrition and medication. The model can explain time courses of erythrocytes, reticulocytes, haemoglobin, haematocrit, red blood cells, EPO, serum iron, ferritin, transferrin saturation, and transferrin under a variety of scenarios including EPO and iron application into healthy volunteers or chemotherapy patients. Unknown model parameters were determined by fitting the predictions of the model to time series data from literature. We demonstrate how the model can be used to make predictions of untested therapy options such as cytotoxic chemotherapy supported by iron and EPO. Following our ultimate goal of establishing a model of anaemia treatment in chronic kidney disease, we aim at translating our model to this pathological condition in the near future.


Asunto(s)
Eritropoyesis/fisiología , Hierro/metabolismo , Modelos Biológicos , Anemia/tratamiento farmacológico , Suplementos Dietéticos , Eritrocitos/citología , Eritrocitos/metabolismo , Eritropoyetina/metabolismo , Eritropoyetina/uso terapéutico , Ferritinas/análisis , Hemoglobinas/análisis , Humanos , Hierro/administración & dosificación
9.
Biochim Biophys Acta Biomembr ; 1862(6): 183231, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32119860

RESUMEN

Aging of red blood cells (RBCs) is associated with alteration in a wide range of RBC features, occurring each on its own timescale. A number of these changes are interrelated and initiate a cascade of biochemical and structural transformations, including band-3 clustering and phosphatidylserine (PS) externalization. Using specific band-3 clustering agents (acridine orange (AO) and ZnCl2), we examined whether treatment of RBCs with these agents may affects PS externalization and whether this process is Ca2+-dependent. RBCs were isolated from the blood of eight healthy donors upon obtaining their informed consent. The suspension was supplemented with increasing concentrations of AO or ZnCl2 (from 0.5 to 2.0 mM) and incubated at 25 °C for 60 min. To detect PS at the RBC surface, we used allophycocyanin-conjugated recombinant human Annexin V. We demonstrated, that treatment of RBCs with both clustering agents caused an elevation in the percent of cells positively labeled by Annexin-V (RBCPS), and that this value was not dependent on the presence of calcium in the buffer: RBCs treated with AO in the presence of either EDTA, EGTA or calcium exhibited similar percentage of RBCPS. Moreover, the active influx of Zn2+ into RBCs induced by their co-incubation with both ZnCl2 and A23187 did not increase the percent of RBCPS as compared to RBCs incubated with ZnCl2 alone. Taken together, these results demonstrate that the band-3 clustering agents (AO or ZnCl2) induce PS externalization in a Ca2+ independent manner, and we hereby suggest a possible scenario for this phenomenon.


Asunto(s)
Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Análisis por Conglomerados , Eritrocitos/citología , Fosfatidilserinas/metabolismo , Naranja de Acridina/farmacología , Anexina A5/metabolismo , Calcio/farmacología , Senescencia Celular , Cloruros/farmacología , Humanos , Compuestos de Zinc/farmacología
10.
Biochemistry (Mosc) ; 85(1): 119-129, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32079523

RESUMEN

Suicidal erythrocyte death, or eryptosis, is the key event in eliciting anemia in numerous pathological conditions, including diabetes, chronic kidney disease, cancer, sepsis, etc. Oxidative stress is an important trigger in the acceleration of erythrocyte loss via eryptosis and an underlying mechanism of anemia emergence in the above pathologies. Therefore, there is an increasing demand for identification of antioxidants and anti-eryptotic agents for the management of stress-related ailments. Here, we demonstrated the antioxidant and anti-eryptotic properties of the tamarind seed coat ethanol extract (TSCEE) against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress and eryptosis. The presence of probable secondary metabolites in the TSCEE extract was investigated by RP-HPLC. Active groups present in the TSCEE were studied by the Fourier-transform infrared spectroscopy. Cyclic voltammetric studies confirmed the antioxidant potential of TSCEE. The protective effect of TSCEE on red blood cells was confirmed by assessing various eryptotic markers, such as reactive oxygen species generation, intracellular calcium levels, and phosphatidylserine exposure. TSCEE reduced lipid peroxidation and protein carbonyl content and restored the levels of glutathione, antioxidant enzymes, and enzymes involved in glutathione replenishment. In conclusion, TSCEE was found to exhibit multiple therapeutic properties, which makes it a promising agent for treating oxidative stress-induced eryptosis and subsequent anemia in various pathologies.


Asunto(s)
Antioxidantes/farmacología , Eriptosis/efectos de los fármacos , Eritrocitos , Extractos Vegetales/farmacología , Tamarindus/metabolismo , Biomarcadores/metabolismo , Calcio/metabolismo , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Glutatión/metabolismo , Humanos , Peroxidación de Lípido , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Semillas/metabolismo
11.
Int J Biol Macromol ; 144: 781-790, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31678100

RESUMEN

The present study investigates the purification, structure and in vitro antioxidant activities of a novel water soluble polysaccharide (LWSP) extracted from Linum usitatissimum L. seeds and evaluates the in vivo wound healing performance on CO2 laser fractional burn in a rat model. LWSP is a heteropolysaccharide that consists of glucose, mannose, xylose and arabinose. Three different tests were used to evaluate the antioxidant activity of this carbohydrate. The scavenging activity against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical at a concentration of 5 mg/ml was 99.77%. The total antioxidant capacity of LWSP at 12 mg/ml was equivalent to 166.61 µg acsorbic acid. LWSP displayed a high protection effect against DNA damage induced byhydroxyl radical. No hemolytic activity was observed towards human erythrocytes. LWSP was tested in functional properties. The results showed good emulsion properties and high water (WHC) and oil holding (OHC) capacities (11.23 and 1.05%, respectively). In addition, the application of LWSP on the burn wound site in rat model increased significantly the percentage of burn contraction (98.6%) after 8 days of injury. According to the histological assessment, the LWSP-treated group had a higher content of hydroxyproline (846. 67 ±â€¯92.28 mg/g tissue) than the other groups. Overall, the findings demonstrate that the application of this novel LWSP may open promising opportunities for burn wound healing in modern medicine.


Asunto(s)
Antioxidantes/química , Quemaduras/tratamiento farmacológico , Lino/química , Extractos Vegetales/química , Polisacáridos/química , Semillas/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Antioxidantes/farmacología , Benzotiazoles/química , Línea Celular , Emulsiones/química , Eritrocitos/citología , Depuradores de Radicales Libres/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Hidroxiprolina/metabolismo , Rayos Láser , Masculino , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Ratas Wistar , Ácidos Sulfónicos/química
12.
Mater Sci Eng C Mater Biol Appl ; 106: 110056, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31753372

RESUMEN

Proanthocyanidins (PCs), a component of grape seed extract (GSE), have recently being used for the treatment of wounds. However, poor absorption, poor stability and rapid elimination from the systemic circulation limit its acceptance. In addressing these problems, we herein report the development of PCs based nanoformulations (PCs/SOLU) for the first time based on 1% GSE and assessed its wound healing potential in-vivo on the wistar rats. GSE and PCs/SOLU nanodispersions 1% were prepared by incorporating them into the ointment base via uniform mixing to form ointment which could be easily applied topically to wounds. The antibacterial activity of PCs/SOLU against gram positive and gram-negative bacteria strains proved that the cell membranes became more permeable with disrupted cell structure. While carrageenan and histamine induced rat paw edema analyses show there was no inflammatory signs in animals treated with 1 wt% of PCs/SOLU nanodispersion. Excision wound measuring about 3 cm in depth was created on the wistar rats. The ointment was applied topically on the wounded site and the wound contraction was measured daily. Grape seed extract (GSE) ointment, ointment base and povidone­iodine (Povi-Iod) ointment of about 1% was used as the control, positive and negative standards. PCs/SOLU nanodispersion heals the wound by mobilising the fibroblasts in the wound site and inhibits the inflammatory response through decreased expression of monocyte. The macroscopical, immunological and histopathological assessments revealed that PCs/SOLU nanodispersion ointment usage improves the cell adhesion and proliferation.


Asunto(s)
Nanoestructuras/química , Pomadas/farmacología , Proantocianidinas/química , Cicatrización de Heridas/efectos de los fármacos , Administración Tópica , Animales , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/patología , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Extracto de Semillas de Uva/química , Hemólisis/efectos de los fármacos , Humanos , Masculino , Pomadas/química , Pomadas/uso terapéutico , Polietilenglicoles/química , Polivinilos/química , Proantocianidinas/farmacología , Proantocianidinas/uso terapéutico , Ratas , Ratas Wistar , Piel/patología
13.
Cell Physiol Biochem ; 53(6): 933-947, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31805226

RESUMEN

BACKGROUND/AIMS: We showed that patho-physiological concentrations of either 7-keto-cholesterol (7-KC), or cholestane-3beta, 5alpha, 6beta-triol (TRIOL) caused the eryptotic death of human red blood cells (RBC), strictly dependent on the early production of reactive oxygen species (ROS). The goal of the current study was to assess the contribution of the erythrocyte ROS-generating enzymes, NADPH oxidase (RBC-NOX), nitric oxide synthase (RBC-NOS) and xanthine oxido-reductase (XOR) to the oxysterol-dependent eryptosis and pertinent activation pathways. METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, reactive oxygen/nitrogen species (RONS) and nitric oxide formation from 2',7'-dichloro-dihydrofluorescein (DCF-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) -dependent fluorescence, respectively; Akt1, phospho-NOS3 Ser1177, and PKCζ from Western blot analysis. The activity of individual 7-KC (7 µM) and TRIOL (2, µM) on ROS-generating enzymes and relevant activation pathways was assayed in the presence of Diphenylene iodonium chloride (DPI), N-nitro-L-arginine methyl ester (L-NAME), allopurinol, NSC23766 and LY294002, inhibitors in this order of RBC-NOX, RBC-NOS, XOR and upstream regulatory proteins Rac GTPase and phosphoinositide3 Kinase (PI3K); hemoglobin oxidation from spectrophotometric analysis. RESULTS: RBC-NOX was the target of 7-KC, through a signaling including Rac GTPase and PKCζ, whereas TRIOL caused activation of RBC-NOS according to the pathway PI3K/Akt, with the concurrent activity of a Rac-GTPase. In concomitance with the TRIOL-induced .NO production, formation of methemoglobin with global loss of heme were observed, ascribable to nitrosative stress. XOR, activated after modification of the redox environment by either RBC-NOX or RBC-NOS activity, concurred to the overall oxidative/nitrosative stress by either oxysterols. When 7-KC and TRIOL were combined, they acted independently and their effect on ROS/RONS production and PS exposure appeared the result of the effects of the oxysterols on RBC-NOX and RBC-NOS. CONCLUSION: Eryptosis of human RBCs may be caused by either 7-KC or TRIOL by oxidative/nitrosative stress through distinct signaling cascades activating RBC-NOX and RBC-NOS, respectively, with the complementary activity of XOR; when combined, the oxysterols act independently and both concur to the final eryptotic effect.


Asunto(s)
Colestanoles/farmacología , Eriptosis/efectos de los fármacos , Cetocolesteroles/farmacología , NADPH Oxidasas/metabolismo , Óxido Nítrico Sintasa/metabolismo , Eritrocitos/citología , Eritrocitos/metabolismo , Hemoglobinas/química , Humanos , Oxidación-Reducción , Fosfatidilinositol 3-Quinasas/química , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al GTP rac/antagonistas & inhibidores , Proteínas de Unión al GTP rac/metabolismo
15.
Biorheology ; 56(4): 221-235, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31640080

RESUMEN

BACKGROUND: RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. OBJECTIVE: In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. METHODS: A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. RESULTS: Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). CONCLUSIONS: Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.


Asunto(s)
Antineoplásicos/farmacología , Azetidinas/farmacología , Neoplasias/sangre , Óxido Nítrico/sangre , Nitritos/farmacología , Nitrocompuestos/farmacología , Biomarcadores/sangre , Deformación Eritrocítica/efectos de los fármacos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Humanos , NG-Nitroarginina Metil Éster/farmacología , Neoplasias/tratamiento farmacológico
16.
Chem Biodivers ; 16(12): e1900428, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31637808

RESUMEN

The present study was performed to assess the HPLC-DAD analysis as well as antioxidant and protective effects of Tunisian Rhanterium suaveolens (Rs) against acetamiprid (ACT) induced oxidative stress on mice erythrocytes. The in vitro assays showed that the methanolic extract of Rs has an impressive antioxidant effect proved by testing the total antioxidant and scavenging activities using BCB, DPPH and ABTS assays, respectively. Moreover, qualitative and quantitative analysis using HPLC-DAD revealed the richness of Rs in polyphenols where p-Coumaric, Apigenin-7-glucoside and Ferulic acid were detected as the most abundant polyphenols. In the in vivo experiment, ACT, used as a toxicity model, was given to mice at a dose of 20 mg/kg. The latter was the origin of hemolytic anemia characterized by a significant decrease in red blood cells, hemoglobin and hematocrit levels and an increase in bilirubin, LDH, osmotic fragility, reticulocytes and white blood cells number. Characteristic erythrocyte morphological alterations were also determined as spherocytosis, schistocytosis and dacryocystitis. The oxidative status of ACT-treated mice was also altered manifested by a significant increase in MDA and GSH levels and a decrease in SOD, CAT and GPx activities. When receiving the Rs methanolic extract at a dose of 300 mg/kg, all the parameters cited above were restored in mice. These remarkable corrections could only confirm the important antioxidant effect and the noticeable protective properties that possess Rs owing to its broad range of secondary bioactive metabolites.


Asunto(s)
Antioxidantes/análisis , Asteraceae/química , Cromatografía Líquida de Alta Presión/métodos , Neonicotinoides/farmacología , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/análisis , Animales , Antioxidantes/química , Antioxidantes/farmacología , Asteraceae/metabolismo , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Flavonoides/química , Flavonoides/farmacología , Ratones , Extractos Vegetales/química , Polifenoles/química , Polifenoles/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Superóxido Dismutasa/metabolismo , Túnez
17.
ACS Appl Mater Interfaces ; 11(44): 41165-41177, 2019 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-31651138

RESUMEN

As a promising biodegradable metallic material, magnesium (Mg) and its alloys have attracted special attention in the recent decade. However, challenges still remain due to its high corrosion rate and insufficient biocompatibility after implantation. In this work, we prepare a simple and versatile green tea phenol-metal induced multilayer conversion coating (Mg2+ incorporated epigallocatechin gallate (EGCG) coating) on magnesium alloys' (AZ31) substrate by layer-by-layer (LBL) method. The surface morphology results revealed that, with the incorporation of Mg2+, the as-formed EGCG/Mg coating was rich in phenol-Mg complex and presented more homogeneous and dense morphology, with far less cracks than the pure EGCG coating. The in vitro degradation rate and corrosion resistance were studied by electrochemical corrosion tests and monitoring of the changed pH value and hydrogen evolution, respectively, which revealed that the corrosion rate was effectively decreased compared to that of bare AZ31 after it was protected by EGCG/Mg coating. In vitro and ex vivo thrombogenicity test demonstrated the EGCG/Mg coatings presented an impressive improvement in decreasing the adhesion and activation of platelets and erythrocytes, in activated partial thromboplastin time (APTT), and in antithrombogenicity compared to those of bare AZ31. Owing to the mild degradation rate, in combination with the biological function of EGCG, enhanced endothelial cells' (ECs') adhesion and proliferation, suppressed smooth muscle cells' (SMCs') adhesion/proliferation, and inhibited cytokine release were observed on EGCG/Mg coated AZ31 alloy. Besides, the in vivo subcutaneous embedding experiment suggested that the EGCG/Mg coating performed more mild tissue response due to the improved corrosion resistance to the surrounding microenvironment. Moreover, for in vivo abdominal aorta assay, the EGCG/Mg coated AZ31 wire presented better corrosion resistance and enhanced re-endothelialization compared to bare AZ31 wire. These results suggested the potential of using green tea polyphenol induced Mg2+-rich multilayer conversion coating for enhanced corrosion protection and desired biocompatibility of biodegradable cardiovascular implants.


Asunto(s)
Aleaciones/química , Catequina/análogos & derivados , Materiales Biocompatibles Revestidos/química , Té/química , Animales , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/patología , Plaquetas/citología , Plaquetas/metabolismo , Catequina/química , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Corrosión , Células Endoteliales/citología , Células Endoteliales/metabolismo , Eritrocitos/citología , Eritrocitos/metabolismo , Eritrocitos/patología , Fibrinolíticos/química , Fibrinolíticos/farmacología , Humanos , Magnesio/química , Activación Plaquetaria/efectos de los fármacos , Prótesis e Implantes , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie , Té/metabolismo
18.
Comput Math Methods Med ; 2019: 9580126, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31354860

RESUMEN

The partial least squares method has many advantages in multivariable linear regression, but it does not include the function of feature selection. This method cannot screen for the best feature subset (referred to in this study as the "Gold Standard") or optimize the model, although contrarily using the L1 norm can achieve the sparse representation of parameters, leading to feature selection. In this study, a feature selection method based on partial least squares is proposed. In the new method, exploiting partial least squares allows extraction of the latent variables required for performing multivariable linear regression, and this method applies the L1 regular term constraint to the sum of the absolute values of the regression coefficients. This technique is then combined with the coordinate descent method to perform multiple iterations to select a better feature subset. Analyzing traditional Chinese medicine data and University of California, Irvine (UCI), datasets with the model, the experimental results show that the feature selection method based on partial least squares exhibits preferable adaptability for traditional Chinese medicine data and UCI datasets.


Asunto(s)
Análisis de los Mínimos Cuadrados , Medicina Tradicional China/estadística & datos numéricos , Análisis Multivariante , Rheum/metabolismo , Algoritmos , Animales , Velocidad del Flujo Sanguíneo , Neoplasias de la Mama/epidemiología , Bases de Datos Factuales , Eritrocitos/citología , Femenino , Humanos , Modelos Lineales , Aprendizaje Automático , Modelos Estadísticos , Ratas , Análisis de Regresión , Choque Cardiogénico/terapia
19.
J Photochem Photobiol B ; 197: 111541, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31272033

RESUMEN

Here, we report the novel fabrication of ZnO nanoparticles using the Costus igneus leaf extract. Gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy to determine the bioactive components present in the plant extract. The synthesis of Ci-ZnO NPs (C. igneus- coated zinc oxide nanoparticles) was accomplished using a cost-effective and simple technique. Ci-ZnO NPs were specified using UV-visible spectroscopy, FTIR, XRD, and TEM. Ci-ZnO NPs was authenticated by UV-Vis and exhibited a peak at 365 nm. The XRD spectra proved the crystalline character of the Ci-ZnO NPs synthesized as hexagonal wurtzite. The FTIR spectrum illustrated the presence of possible functional groups present in Ci-ZnO NPs. The TEM micrograph showed evidence of the presence of a hexagonal organization with a size of 26.55 nm typical of Ci-ZnO NPs. The α-amylase and α-glucosidase inhibition assays demonstrated antidiabetic activity of Ci-ZnO NPs (74 % and 82 %, respectively), and the DPPH [2,2-diphenyl-1-picrylhydrazyl hydrate] assay demonstrated the antioxidant activity of the nanoparticles (75%) at a concentration of 100 µg/ml. The Ci-ZnO NPs exhibited promising antibacterial and biofilm inhibition activity against the pathogenic bacteria Streptococcus mutans, Lysinibacillus fusiformis, Proteus vulgaris, and Vibrio parahaemolyticus. Additionally, the Ci-ZnO NPs showed biocompatibility with mammalian RBCs with minimum hemolytic activity (0.633 % ±â€¯0.005 %) at a concentration of 200 µg/ml.


Asunto(s)
Antibacterianos/farmacología , Antioxidantes/química , Biopelículas/efectos de los fármacos , Nanopartículas del Metal/química , Extractos Vegetales/química , Óxido de Zinc/química , Antibacterianos/síntesis química , Antibacterianos/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Costus/química , Costus/metabolismo , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/fisiología , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/fisiología , Tecnología Química Verde , Hemólisis/efectos de los fármacos , Humanos , Insulina/química , Nanopartículas del Metal/toxicidad , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Extractos Vegetales/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo
20.
Bol. latinoam. Caribe plantas med. aromát ; 18(4): 359-377, jul. 2019. tab
Artículo en Inglés | LILACS | ID: biblio-1008174

RESUMEN

Plant species have been used for therapeutic purposes since ancient times and are still in use today since these products represent a source of raw material for the production of phytotherapeutic formulations. Screening and investigation of plants with pharmacological potential require the evaluation of characteristics related to their action, efficacy and safety in different steps. Among these steps, pre- clinical trials are used to evaluate the properties of the test product in in vitro experiments, such as cytotoxicity assays. Within this context, this study consists of a bibliometric analysis of some in vitro cytotoxicity and toxicity assays in erythrocytes used during bioprospecting of medicinal plants. The results demonstrated the wide application of erythrocytes to evaluate the biological effects of medicinal plant extracts. The methods were found to be valid and effective for the preliminary investigation of the in vitro cytotoxicity and toxicity of plant products.


El uso de especies vegetales para fines terapéuticos es una práctica histórica y todavía bastante actual, ya que estos productos pueden representar una fuente de materia prima para la producción de formulaciones fitoterápicas. En investigación de plantas con potencial farmacológico requiere la evaluación de su acción, eficacia y seguridad, a través de diferentes etapas. Entre estas, en los ensayos preclínicos se evalúan las propiedades del producto-prueba en experimentos in vitro, tales como ensayos de citotoxicidad, entre otros. En este aspecto, el presente estudio consiste en un análisis bibliométrico acerca de algunas pruebas de citotoxicidad y toxicidad in vitro en eritrocitos realizados en los ensayos de bioprospección de plantas medicinales. Los resultados evidencian la amplia utilización de eritrocitos para la evaluación de los efectos biológicos de extractos de plantas medicinales, apuntándolos como métodos válidos y eficaces para la investigación preliminar de la citotoxicidad y toxicidad in vitro de productos vegetales.


Asunto(s)
Bioensayo/métodos , Extractos Vegetales/toxicidad , Eritrocitos/efectos de los fármacos , Antioxidantes/toxicidad , Fragilidad Osmótica , Estrés Oxidativo , Eritrocitos/citología , Bioprospección , Hemólisis/efectos de los fármacos
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