RESUMEN
Long thermal oxidative kinetic and stability of four different edible oils (colza, corn, frying, sunflower) from various brands were surveyed with the use of attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) combined with multivariate curve resolution-alternative least square (MCR-ALS). Sampling from the heated oils (at 170 °C) was performed each 3 h during a 36-h period. Changes in the ATR-FTIR spectra of the oil samples in the range of 4000-550 cm-1 were followed as a function of heating time. MCR-ALS was utilized to resolve the concentration and spectral profiles of three detected kinetic components. Three variations in resolved concentration profiles were related to the thermal-deduction of triacylglycerol of unsaturated acid, appearance of hydroperoxides form of triacylglycerols and generation of secondary oxidation products. The kinetic profiles of these species were dependent on the type of oil. The proposed method can define a new way to monitor the oils' quality.
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The antibiotic residues in milk are a well-known serious problem and pose several health hazards to consumers. We have described a simple, rapid, and inexpensive DLLME-HPLC/UV technique for the extraction of chloramphenicol and florfenicol residues in milk samples. Under the optimum conditions, linearity of the method was observed over the range 0.02-0.85 µg/L with correlation coefficients > 0.999. The proposed method has been found to have a good limit of detection (signal to noise ratio = 3) for chloramphenicol (12.5 µg/Kg) and florfenicol (12.2 µg/Kg), and precision with relative standard deviation values under 15% (RSD, n = 3). Good recoveries (69.1-79.4%) were obtained for the extraction of the target analytes in milk samples. This simple and economic method has been applied for analyses of 15 real milk samples. Among all samples only one of them was contaminated to florfenicol; 62.4 µg/Kg and contamination to chloramphenicol was not detected.
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2,3-Butanediol (2,3-BD) is a valuable bulk chemical owing to its extensive application in chemical and pharmaceutical industry with diverse applications in drug, cosmetics and food products. In the present study, the biotransformation of acetoin to 2,3-BD by five plant species (Brassica oleracea, Brassica rapa, Daucuscarota, Pastinaca sativa, and Raphnussativus) and five microorganisms (Aspergillusfoetidus, Penicillumcitrinum, Saccharomyces carlbergensis, Pichiafermentans, and Rhodotrulaglutinis) was investigated as a method for the production of 2,3-BD, which can serve as an alternative to the common pentoses and hexoses fermentation by microorganisms. The produced 2,3-BD stereoisomers were characterized and their total conversion yields were determined. The results showed that the examined plants can be used as a green factory for the production of all 2,3-BD stereoisomers, except B. rapa. In microorganisms, P. fermentans and S. carlbergensis produced (-)-2R,3R and mesobutanediol, while P. citrinum produced (+)-2S,3S and mesobutanediol. R. glutinis and A. foetidus produced all three isomers. In conclusion, efficient whole-cell biocatalysts from plants and microorganisms were determined in the bioconversion of acetoin to 2,3-BD. The profile of produced stereoisomers demonstrated that microorganisms produce more specific stereoisomers.
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A method based on dispersive liquid-liquid microextraction (DLLME) was developed for the quantitative extraction of Ochratoxin A (OTA) from raisin samples. The influence of various parameters on the recovery of OTA such as type and volume of DLLME extractant, centrifuging and sonication time, also volume of deionized water was investigated. Recovery values under the optimum conditions were between 68.6 and 85.2 %, the inner and intra-day precision expressed as relative standard deviation (RSD%, n = 3), were less than 15 % at spiking levels of 2.5-30 µg kg(-1). Linearity was studied from 0.5 to 30 µg L(-1), and the limits of detection (LOD) and quantification (LOQ) were 0.7 and 2.0 µg kg(-1), respectively. Real samples were analyzed by DLLME method and compared with confirmative immunoaffinity Column Chromatography (IAC) clean-up. Low cost, simplicity of operation, speed and minimum consumption of organic solvent were the main advantages of proposed method. The mean contamination of samples was 0.88 µg kg(-1) that was lower than European Legal Limit.
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Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure-activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5-25 µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77-15.60 µM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents.
Asunto(s)
Antineoplásicos/farmacología , Dihidropiridinas/farmacología , Diseño de Fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Subfamilia B de Transportador de Casetes de Unión a ATP/antagonistas & inhibidores , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacología , Antineoplásicos/efectos adversos , Antineoplásicos/síntesis química , Antineoplásicos/química , Transporte Biológico/efectos de los fármacos , Canales de Calcio/química , Canales de Calcio/metabolismo , Línea Celular Tumoral , Dihidropiridinas/efectos adversos , Dihidropiridinas/síntesis química , Dihidropiridinas/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
ß-site amyloid precursor protein cleaving enzyme (BACE-1) is a validated target for Alzheimer therapy due to its distinctive role in pathogenesis of AD. In the present contribution, a series of new 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structures were synthesized as BACE-1 inhibitors (6a-6n). In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer assay. Synthesized dihydropyridine (DHP) analogues exhibited weak to good inhibitory activities while 6i, 6n and 6a were found to be the most potent molecules with 83.76, 79.45 and 72.47 % BACE-1 inhibition at 10 µM, respectively. Structure binding/activity relationship elucidations revealed that superior BACE-1 inhibitory activities were observed for DHP derivatives bearing fused/non-fused thiazole groups and particularly 3,5-bis-N-(6-ethoxy-2-benzothiazolyl) moiety. Binding maps showed that enhanced activity may be attributed to the additional H-bond and hydrophobic interactions with S2-S3 subpockets of BACE-1.
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Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Dihidropiridinas/química , Dihidropiridinas/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/enzimología , Cristalografía por Rayos X , Dihidropiridinas/uso terapéutico , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Relación Estructura-ActividadRESUMEN
A functional polycation nanonetwork was developed for delivery of water soluble chemotherapeutic agents. The complexes of polyethyleneimine grafted methoxy polyethylene glycol (PEI-g-mPEG) and Zn(2+) were utilized as the micellar template for cross-linking with dithiodipropionic acid, followed by an acidic pH dialysis to remove the metal ion from the micellar template. The synthesis method was optimized according to pH, the molar ratio of Zn(2+), and the cross-link ratio. The atomic force microscopy showed soft, discrete, and uniform nano-networks. They were sensitive to the simulated reductive environment as determined by Ellman's assay. They showed few positive ζ potential and an average hydrodynamic diameter of 162±10 nm, which decreased to 49±11 nm upon dehydration. The ionic character of the nano-networks allowed the achievement of a higher-loading capacity of methotrexate (MTX), approximately 57% weight per weight, depending on the cross-link and the drug feed ratios. The nano-networks actively loaded with MTX presented some suitable properties, such as the hydrodynamic size of 117±16 nm, polydispersity index of 0.22, and a prolonged swelling-controlled release profile over 24 hours that boosted following reductive activation of the nanonetwork biodegradation. Unlike the PEI ionomer, the nano-networks provided an acceptable cytotoxicity profile. The drug-loaded nano-networks exhibited more specific cytotoxicity against human hepatocellular carcinoma cells if compared to free MTX at concentrations above 1 µM. The enhanced antitumor activity in vitro might be attributed to endocytic entry of MTX-loaded nano-networks that was found in the epifluorescence microscopy experiment for the fluorophore-labeled nano-networks.
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Supervivencia Celular/efectos de los fármacos , Emulsiones/química , Metotrexato/administración & dosificación , Metotrexato/química , Nanocápsulas/química , Nanocápsulas/ultraestructura , Polietileneimina/química , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/química , Reactivos de Enlaces Cruzados/química , Difusión , Células Hep G2 , Humanos , Ensayo de Materiales , Micelas , Nanocápsulas/administración & dosificación , Oxidación-Reducción , Tamaño de la PartículaRESUMEN
Alzheimer disease (AD) is a neuronal dementia for which no treatment has been consolidated yet. Major pathologic hallmark of AD is the aggregated extracellular amyloid-ß plaques in the brains of disease sufferers. Aß-peptide is a major component of amyloid plaques and is produced from amyloid precursor protein (APP) via the proteolysis action. An aspartyl protease known as ß-site amyloid precursor protein cleaving enzyme (BACE-1) is responsible for this proteolytic action. Distinctive role of BACE-1 in AD pathogenesis has made it a validated target to develop anti-Alzheimer agents. Our structure-based virtual screening method led to the synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine BACE-1 inhibitors (6a-6p; in vitro hits). Molecular docking and DFT-based ab initio studies using B3LYP functional in association with triple-ζ basis set (TZV) proposed binding mode and binding energies of ligands in the active site of the receptor. In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer (FRET) assay. Most of the synthesized dihydropyridine scaffolds were active against BACE-1 while 6d, 6k, 6n and 6a were found to be the most potent molecules with IC50 values of 4.21, 4.27, 4.66 and 6.78 µM, respectively. Superior BACE-1 inhibitory activities were observed for dihydropyridine derivatives containing fused/nonfused thiazole containing groups, possibly attributing to the additional interactions with S2-S3 subpocket residues. Relatively reliable correlation between calculated binding energies and experimental BACE-1 inhibitory activities was achieved (R(2)=0.51). Moreover, compounds 6d, 6k, 6n and 6a exhibited relatively no calcium channel blocking activity with regard to nifedipine suggesting them as appropriate candidates for further modification(s) to BACE-1 inhibitory scaffolds.
Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Carbamatos/química , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Piridinas/química , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Sitios de Unión , Bloqueadores de los Canales de Calcio/síntesis química , Bloqueadores de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/metabolismo , Dominio Catalítico , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Cobayas , Humanos , Enlace de Hidrógeno , Masculino , Simulación del Acoplamiento Molecular , Unión Proteica , Piridinas/síntesis química , Piridinas/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , TermodinámicaRESUMEN
Multidrug resistance (MDR) is an important obstacle that limits the efficacy of chemotherapy in many types of cancer. In this study, 14 novel asymmetrical DHPs possessing pyridyl alkyl carboxylate substitutions at C3 and alkyl carboxylate groups at C5 in addition to a nitroimidazole or nitrophenyl moiety at C4 position were synthesized. Calcium channel blocking (CCB) activity was measured in guinea pig ileal longitudinal smooth muscle. Cytotoxicity was tested on 4 human cancer cell lines, while MDR reversal capacity was examined on P-glycoprotein overexpressing doxorubicin resistant MES-SA-DX5 and compared with non-resistant MES-SA cells. Compounds showed different CCB (IC50: 29.3 nM-4.75 µM) and cytotoxic activities (IC50: 6.4 to more than 100 µM). Several compounds having nitrophenyl moiety at C4, could significantly reverse resistance to doxorubicin at 0.5 and 1 µM. The most active ones were 7e and 7g containing ethyl carboxylate and isopropyl carboxylate at C5, respectively. CCB activity, which is considered an undesirable effect for these agents, of 7e and 7g were 33 and 20 times lower than nifedipine, respectively. In conclusion, the newly synthesized asymmetrical DHP compounds showed promising MDR reversal and antitumoral activities with low CCB effects and could be of therapeutic value in drug resistant cancer.
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Dihidropiridinas/química , Dihidropiridinas/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Bloqueadores de los Canales de Calcio/síntesis química , Bloqueadores de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/farmacología , Línea Celular Tumoral , Dihidropiridinas/síntesis química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Cobayas , Humanos , Concentración 50 Inhibidora , Masculino , Relación Estructura-ActividadRESUMEN
By using FT-IR spectroscopy, many researchers from different disciplines enrich the experimental complexity of their research for obtaining more precise information. Moreover chemometrics techniques have boosted the use of IR instruments. In the present study we aimed to emphasize on the power of FT-IR spectroscopy for discrimination between different oil samples (especially fat from vegetable oils). Also our data were used to compare the performance of different classification methods. FT-IR transmittance spectra of oil samples (Corn, Colona, Sunflower, Soya, Olive, and Butter) were measured in the wave-number interval of 450-4000 cm(-1). Classification analysis was performed utilizing PLS-DA, interval PLS-DA, extended canonical variate analysis (ECVA) and interval ECVA methods. The effect of data preprocessing by extended multiplicative signal correction was investigated. Whilst all employed method could distinguish butter from vegetable oils, iECVA resulted in the best performances for calibration and external test set with 100% sensitivity and specificity.
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Grasas/análisis , Modelos Químicos , Aceites de Plantas/análisis , Análisis Discriminante , Análisis de los Mínimos Cuadrados , Análisis Multivariante , Análisis de Componente Principal , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
OBJECTIVES: The effects of Anethum graveolens seed extract on fertility of male rats were investigated. METHODS: Male Wistar rats were divided into five groups according to the treatment they received during 42 days: control, low dose (0.5 g/kg) and high dose (5 g/kg) of aqueous extracts, and low dose (0.045 g/kg) and high dose (0.45 g/kg) of ethanol extracts of Anethum graveolens seed. Sperm count and motility and testosterone concentration were measured. Sections of the testes, epididymis, and seminal vesicles were stained with peroxidase-conjugated lectins of Ulex europaeus agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soy bean agglutinin and concanavalin A. The treated male rats were mated with females and the crown-rump lengths and weights of their newborn pups were measured. RESULTS: No significant differences in sperm count, sperm motility or testosterone concentration were observed in the experimental groups. However, female rats did not become pregnant after mating with rats given the high dose of the ethanol extract. The distribution of terminal sugars on the epithelial surface of the reproductive structures decreased in the experimental groups. CONCLUSION: Anethum graveolens extract decreased fertility rate by modifying some terminal sugars on the cell surface of male reproductive organs involved in sperm maturation, capacitation and oocyte recognition.
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Anethum graveolens , Epidídimo/química , Fertilidad/efectos de los fármacos , Extractos Vegetales/farmacología , Vesículas Seminales/efectos de los fármacos , Testículo/efectos de los fármacos , Acetilgalactosamina/análisis , Análisis de Varianza , Animales , Epidídimo/anatomía & histología , Epidídimo/efectos de los fármacos , Femenino , Fucosa/análisis , Galactosa/análisis , Tamaño de la Camada/efectos de los fármacos , Masculino , Manosa/análisis , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Embarazo , Ratas , Ratas Wistar , Semillas , Vesículas Seminales/anatomía & histología , Vesículas Seminales/química , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Testículo/anatomía & histología , Testículo/química , Testosterona/sangreRESUMEN
Plants may have the ability to modulate immune responses. In the present study, the effects of three plants belonging to Labiatae family, each traditionally used for the treatments of infections and inflammatory diseases, as well as the role of thymol (as one the major components of these plants), were investigated for their potential to affect the activation of lymphocytes. Four organic extracts of Thymus vulgaris and two other plants (i.e., T. daenensis and Zataria multiflora) were prepared. The effect of the extracts on mitogen (PHA)-stimulated peripheral blood lymphocytes was determined using a cell proliferation assay. The hexane extracts obtained from the three plants showed the strongest inhibitory effects on PHA-induced proliferation. Use of preparative thin layer and gas chromatographies in conjunction with the proliferation assay confirmed that thymol was the major component responsible for the observed effects from the three plants. Thymol inhibited inducible lymphocyte proliferation in a concentration-dependent manner, with reductions ranging from 62.8% at 50 µg/ml to 89.8% at 200 µg/ml (> 0.1 µg/ml (p < 0.01). Flow cytometric analysis using propidium iodide staining showed that the inhibitory effect of thymol at 200 µg/ml was due to a cytotoxic activity. In conclusion, the three Labiatae plants studied here each showed immunosuppressive effects against lymphocytes and it was most likely that thymol was the compound in these plants responsible for this effect.
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Factores Inmunológicos/farmacología , Lamiaceae/química , Linfocitos/efectos de los fármacos , Adulto , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fraccionamiento Químico , Cromatografía de Gases , Cromatografía en Capa Delgada , Formazáns/metabolismo , Humanos , Células Jurkat , Linfocitos/inmunología , Linfocitos/metabolismo , Masculino , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sales de Tetrazolio/metabolismo , Timol/análisis , Timol/farmacología , Thymus (Planta)/químicaRESUMEN
OBJECTIVE: End-stage renal disease (ESRD) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence, and is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor-ß (TGF-ß) may contribute to the development of ESRD in patients with diabetic nephropathy. Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-ß. Therefore, this study investigated the effects of turmeric on serum and urinary TGF-ß, interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α), as well as proteinuria, in patients with overt type 2 diabetic nephropathy. MATERIAL AND METHODS: A randomized, double-blind and placebo-controlled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy, randomized into a trial group (n = 20) and a control group (n = 20). Each patient in the trial group received one capsule with each meal containing 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (three capsules daily) for 2 months. The control group received three capsules identical in colour and size containing starch for the same 2 months. RESULTS: Serum levels of TGF-ß and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values. No adverse effects related to turmeric supplementation were observed during the trial. CONCLUSION: Short-term turmeric supplementation can attenuate proteinuria, TGF-ß and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients.
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Curcuma , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Interleucina-8/análisis , Fitoterapia , Proteinuria/tratamiento farmacológico , Factor de Crecimiento Transformador beta/análisis , Factor de Necrosis Tumoral alfa/análisis , Administración Oral , Nefropatías Diabéticas/etiología , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteinuria/etiologíaRESUMEN
In the present study, the immunomodulatory effects of Galium mite, a native herb used for the treatment of inflammation in Iranian traditional medicine, was investigated. The methanolic extract of the plant was prepared and examined for in vivo cell-mediated and humoral immunity against antigen in mice. Galium mite stimulated delayed type hypersensitivity at lower concentrations and inhibited the reaction at higher ones (p < 0.05). A dose-related decrease in primary and secondary antibody titer was observed in mice treated with the extract (p < 0.006). The extract at higher concentrations significantly reduced the proliferation of human-activated lymphocytes (p < 0.001). Cell cycle analysis on human lymphocytes treated with the extract showed an increase in the number of cells in sub-G1 region, indicating the ability of the extract to induce apoptosis in these cells. Induction of apoptosis was confirmed by DNA laddering on gel electrophoresis. In conclusion, G. mite has the ability to modulate cellular and humoral immune responses to the antigenic challenge and affect the rate of cell proliferation due to induction of apoptosis in the lymphocytes.
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Galium/química , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Metanol/química , Extractos Vegetales/química , Extractos Vegetales/inmunología , Animales , Anticuerpos/inmunología , Apoptosis , Proliferación Celular , Humanos , Hipersensibilidad Tardía/inmunología , Inyecciones Subcutáneas , Linfocitos/citología , Linfocitos/inmunología , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , OvinosRESUMEN
The 1,4-dihydropyridine (DHP) derivatives are a known class of calcium channel blockers. Some derivatives of DHP showed significant cytotoxicity. It was shown that this effect may not be the result of interaction with Ca(2+) channels. In this study, we performed an investigation about the intrinsic cytotoxicity of some derivatives of DHP containing nitroimidazole moiety on their C4 position on four different cancer cell lines (Raji, K562, Fen and HeLa). The result showed that these compounds had moderate-good cytotoxic activity. In addition, QSAR model shows the importance of N atom in cytotoxicity; Ca(2+) channels.
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In this study, the immunomodulatory effects of Salvia mirzayanii were investigated. Study of the effect of this plant on activated human peripheral blood lymphocytes showed stimulatory effects at lower concentrations and inhibitory effects at higher ones (p < 0.01). In flow cytometry analysis, accumulation of apoptotic cells in the sub-G1 phase of the cell cycle of the mitogen-treated lymphocytes exposed to the inhibitory doses of the extract was observed. DNA fragmentation analysis of these cells showed a typical DNA laddering. Immunisation of extract-treated mice with the antigen decreased delayed hypersensitivity skin reaction as well as the antibody titre at higher concentrations (p < 0.007). These results indicated the presence of immunomodulatory compounds in the extract of S. mirzayanii and suggest that the induction of apoptosis in lymphocytes might be the mechanism responsible for the inhibitory effect of the extract that was observed at higher concentrations.
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Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Hipersensibilidad Tardía/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Fitoterapia , Salvia , Adulto , Animales , Formación de Anticuerpos , Canfanos , Células Cultivadas , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/farmacología , Humanos , Interleucina-2/análisis , Masculino , Ratones , Ratones Endogámicos BALB C , Panax notoginseng , Plantas Medicinales , Salvia miltiorrhiza , Adulto JovenRESUMEN
The antioxidant activities of the methanolic extracts of 9 Salvia species and 15 other Lamiaceae plants growing in Iran were evaluated using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. FRAP values ranged form 8.5 to 79.0 microM quercetin equivalents/g dry weight, and IC50 values in the DPPH assay from 115.7 to 1350.2 microg dry weight/mL. Salvia species showed the highest antioxidant activities. S. santolinifolia, S. eremophila and S. palestina, which have not been studied before, were the most active plants. These were more active than the previously studied species from this family, such as S. multicaulis and Marrubium vulgare. S. hydrangea and Gontscharovia popovii also showed high antioxidant activities. FRAP and DPPH assay results showed good correlations with the total phenolic contents of the plants, measured by the Folin-Ciocalteau assay (r2 = 0.925 and 0.799, respectively, p < 0.0001). In conclusion, our study shows that some Lamiaceae plants growing in Iran represent good potential sources of natural antioxidants useful for either prevention or treatment of oxidative stress-related diseases.
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Antioxidantes/química , Lamiaceae/química , Fenoles/química , Depuradores de Radicales Libres , IránRESUMEN
Investigations were carried out to determine antimicrobial and antioxidant properties and total phenol content of three wild species of Ephedra compared with their respective callus cultures. Callus induction was performed in a standard Murashige and Skoog (MS) medium with the following hormonal ranges (mg/L) for every species NAA:1.5, Kin:1 for Ephedra strobiliacea, NAA:2, Kin:1 for Ephedra procera and NAA:2, Kin:0.5 for Ephedra pachyclada. These ranges of PGPR (Plant Growth Promote Regulators) were chosen based on callus induction rates, RGR (Relative Growth Rate) and their fresh weights. An antimicrobial test against five gram negative and two gram positive bacteria and two fungi was performed using the disc diffusion method. All methanolic extracts showed antimicrobial activity, but the antimicrobial activity of the callus cultures was lower than those of the wild plants. E. strobilacea showed the highest antimicrobial activity, and all methanolic extracts of the wild plants and callus cultures unexpectedly showed the highest antimicrobial activity against Pseudomonas aeruginosa. A FRAP (Ferric Reducing Antioxidant Power) test was conducted to evaluate extracts for antioxidant activity. E. strobilacea with 1.61 +/- 0.08 mmol eq quercetin/g extract and 0.278 +/- 0.02 mmol eq quercetin/g extract for the wild plant and callus, respectively, showed the highest results.The total phenol content of extracts was measured by a Folin Ciocalteau test. All the chosen species displayed phenol contents but E. strobilacea had the highest amount (504.9 +/- 41.51 micromol eq catechin/g extracts and 114.61 +/- 15.13 micromol eq catechin/g extracts for the wild plants and callus, respectively).
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Antioxidantes/farmacología , Ephedra/química , Extractos Vegetales/farmacología , Células Cultivadas , Pruebas de Sensibilidad Microbiana , Especificidad de la EspecieRESUMEN
Acetaminophen is one of the most popular analgesic and antipyretic drugs and its overdose, which can cause severe damage to liver and kidneys, is one of the most common reasons of emergency admissions. In this study we investigated the effects of curcumin, derived from plant Curcuma longa, on acetaminophen toxicity, and the possibility of combining therapy of curcumin and N-acetyl cysteine (NAC) to treat this toxicity. The experiments were conducted on 72 male Sprague-Dawley rats randomly divided into 12 groups. Control group was left without treatment, and the other groups were treated with different combinations of acetaminophen, curcumin and NAC. 15min after intraperitoneal injection, the blood level of curcumin was measured using HPLC. Blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), blood urea nitrogen and creatinine were determined 18 and 42h after acetaminophen injection. One week later, the left kidney and the caudate lobe of the liver were harvested to assay glutathione peroxidase, catalase and malondialdehyde. The right kidney and the remaining lobes of the liver were used for histopathology. Analysis of organ function and oxidation parameters showed that curcumin significantly reduced toxic effects of acetaminophen on the liver and kidneys in a dose-dependent manner and significantly potentiated the protective effects of NAC. These findings were confirmed by histopathology. It is concluded that curcumin can protect the liver and kidney from the damage caused by acetaminophen overdose. Moreover, curcumin has the potential to be used in a combination therapy with NAC, significantly decreasing the therapeutic dose of NAC and therefore its side-effects.
Asunto(s)
Acetaminofén/toxicidad , Acetilcisteína/farmacología , Curcumina/farmacología , Enfermedades Renales/prevención & control , Riñón/efectos de los fármacos , Hepatopatías/prevención & control , Hígado/efectos de los fármacos , Animales , Biomarcadores/sangre , Catalasa/metabolismo , Curcumina/metabolismo , Sinergismo Farmacológico , Glutatión Peroxidasa/metabolismo , Riñón/metabolismo , Riñón/patología , Hígado/metabolismo , Hígado/patología , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Pruebas SerológicasRESUMEN
Bioassay-guided fractionation of Haplophyllum canaliculatum Boiss. (Rutaceae) extract resulted in isolation of five quinoline alkaloids: 7-isopentenyloxy-gamma-fagarine, atanine, skimmianine, flindersine and perfamine. This is the first isolation of these compounds from this endemic species. The antitumor activity of these five isolates was evaluated against RAJI, Jurkat, KG-1a, HEP-2, MCF-7, HL-60 and HL-60/MX1 tumor cell lines. The highest cytotoxic effect was observed on acute lymphoblastic leukemia cell lines. 7-Isopentenyloxy-gamma-fagarine, atanine, skimmianine and flindersine exhibited very high cytotoxicity against the RAJI cell line with IC(50) values of 1.5, 14.5, 15.6 and 14.9 microg/mL, respectively and 7-isopentenyloxy-gamma-fagarine, atanine and skimmianine exhibited very high cytotoxicity against the Jurkat cell line with IC(50) values of 3.6, 9.3 and 11.5 microg/mL, respectively. 7-Isopentenyloxy-gamma-fagarine was also highly cytotoxic against the MCF-7 cell line (IC(50) = 15.5 microg/mL), while atanine, skimmianine, flindersine and perfamine showed moderate to low activity against these cells. All alkaloids had moderate to low cytotoxicity against KG-1a and HEP-2. Investigation of the toxic potential of the alkaloids on HL-60 and HL-60/MX1 showed a significantly higher effect against HL-60/MX1, a multidrug-resistant cell line, compared with the control etoposide (p < 0.05). In all cytotoxicity experiments, peripheral blood mononuclear cells (PBMC) were used as a control for normal hematopoietic cells. Flow cytometry analysis of the compounds resulted in the arrest of cell cycle progression at the sub-G1 phase of the RAJI and Jurkat cell lines in a dose-dependent manner. According to computational analyses, the similar cytotoxic trend in the cell lines could be indicative of the fact that these compounds may act through parallel mechanisms.