RESUMEN
Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are becoming more prevalent and an increasing burden on society. Neurodegenerative diseases often arise in the milieu of neuro-inflammation of the brain. Reactive astrocytes are key regulators in the development of neuro-inflammation. This study describes the effects of Palm Fruit Bioactives (PFB) on the behavior of human astrocytes which have been activated by IL-1ß. When activated, the astrocytes proliferate, release numerous cytokines/chemokines including TNFα, RANTES (CCL5), IP-10 (CXCL10), generate reactive oxygen species (ROS), and express specific cell surface biomarkers such as the Intercellular Adhesion Molecule (ICAM), Vascular Cellular Adhesion Molecule (VCAM) and the Neuronal Cellular Adhesion Molecule (NCAM). Interleukin 1-beta (IL-1ß) causes activation of human astrocytes with marked upregulation of pro-inflammatory genes. We show significant inhibition of these pro-inflammatory processes when IL-1ß-activated astrocytes are exposed to PFB. PFB causes a dose-dependent and time-dependent reduction in specific cytokines: TNFα, RANTES, and IP-10. We also show that PFB significantly reduces ROS production by IL-1ß-activated astrocytes. Furthermore, PFB also reduces the expression of ICAM and VCAM, both in activated and naïve human astrocytes in vitro. Since reactive astrocytes play an essential role in the neuroinflammatory state preceding neurodegenerative diseases, this study suggests that PFB may have a potential role in their prevention and/or treatment.
Asunto(s)
Arecaceae/química , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CXCL10/metabolismo , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Frutas/química , Humanos , Interleucina-1beta/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.
Asunto(s)
Modelos Animales de Enfermedad , Fenoles/uso terapéutico , Aceites de Plantas/uso terapéutico , Animales , Arritmias Cardíacas/prevención & control , Aterosclerosis/prevención & control , Presión Sanguínea , Diabetes Mellitus Tipo 2/prevención & control , Masculino , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/deficiencia , Aceite de Palma , Aceites de Plantas/química , Conejos , Ratas , Ratas Endogámicas WKYRESUMEN
Waste from agricultural products represents a disposal liability, which needs to be addressed. Palm oil is the most widely traded edible oil globally, and its production generates 85 million tons of aqueous by-products annually. This aqueous stream is rich in phenolic antioxidants, which were investigated for their composition and potential in vitro biological activity. We have identified three isomers of caffeoylshikimic acid as major components of oil palm phenolics (OPP). The 2,2-diphenyl-1-picrylhydrazyl assay confirmed potent free radical scavenging activity. To test for possible cardioprotective effects of OPP, we carried out in vitro LDL oxidation studies as well as ex vivo aortic ring and mesenteric vascular bed relaxation measurements. We found that OPP inhibited the Cu-mediated oxidation of human LDL. OPP also promoted vascular relaxation in both isolated aortic rings and perfused mesenteric vascular beds pre-contracted with noradrenaline. To rule out developmental toxicity, we performed teratological studies on rats up to the third generation and did not find any congenital anomalies. Thus, these initial studies suggest that OPP is safe and may have a protective role against free radical damage, LDL oxidation and its attendant negative effects, as well as vascular constriction in mitigating atherosclerosis. Oil palm vegetation liquor thus represents a new source of phenolic bioactives.
Asunto(s)
Fenoles/análisis , Aceites de Plantas/química , Animales , Antioxidantes/análisis , Antioxidantes/farmacología , Aorta/efectos de los fármacos , Aorta/fisiología , Compuestos de Bifenilo/química , Cromatografía Líquida de Alta Presión , Técnicas In Vitro , Lipoproteínas LDL/metabolismo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Mesenterio/efectos de los fármacos , Mesenterio/fisiología , Oxidación-Reducción , Aceite de Palma , Fenoles/toxicidad , Picratos/química , RatasRESUMEN
Micellization and solution properties of the aglycon triterpenoids asiatic acid (AA) and madecassic acid (MA) were examined experimentally and in computational simulations. AA and MA belong to the large class of bioactive aglycon triterpenoids, for which limited physicochemical data are available. In this study, solubility, partition coefficient, critical micelle concentrations (CMC), and surface tensions of AA and MA were measured. Reverse phase HPLC data, supported by dye probe experiments and drop shape analysis, showed the CMC in phosphate buffered saline (PBS) to be 15+/-2 microM, and 86+/-9 microM for AA and MA, respectively. The surface tensions of AA and MA in PBS were 64.1 and 64.4 mN/m, respectively. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry indicated the aggregation numbers of AA and MA to be 5 to 7. Molecular dynamics simulations confirmed that molecular association could occur between 5 and 7 molecules in solution. The IC(50) of AA and MA on human small cell carcinoma and human glioblastoma cell lines was 25+/-5 microM and 66+/-13 microM, respectively. The IC(50) is within the range of calculated CMC of AA and MA in bioassay media, suggesting that the micellar aggregates may lead to their cytotoxicity.
Asunto(s)
Micelas , Triterpenos/química , Bioensayo , Carcinoma de Células Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Simulación por Computador , Glioblastoma/tratamiento farmacológico , Humanos , Concentración 50 Inhibidora , Neoplasias Pulmonares/tratamiento farmacológico , Conformación Molecular , Triterpenos Pentacíclicos , Solubilidad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Tensión Superficial , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaAsunto(s)
Antiinfecciosos/metabolismo , Técnicas de Transferencia de Gen , Transferencia de Gen Horizontal , Rhodococcus/metabolismo , Streptomyces/metabolismo , Estreptomicina/química , Antiinfecciosos/química , Biotecnología/métodos , Diseño de Fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas/métodos , Modelos Biológicos , Modelos Químicos , Conformación MolecularRESUMEN
A polyacetylene compound was isolated from the aerial parts of Centella asiatica. The chemical structure of this new compound was identified as methyl 5-[(E)-9-hydroxy-1-(1-hydroxyhexyl)-2-methoxyundeca-3,10-diene-5,7-diynyloxy]pentanoate (cadiyenol). This compound induces apoptosis (63%) independent of cell cycle regimen in mouse lymphoma cells (P388D1) at 28 microM (IC (50) = 24 +/- 2 microM) in 24 hours. The compound also reduces nitric oxide production by 70 +/- 2% in lipopolysacharride-activated mouse macrophages at 24 microM with no measurable cytotoxicity.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Centella , Fitoterapia , Extractos Vegetales/farmacología , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Línea Celular Tumoral/efectos de los fármacos , Humanos , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Poliinos/administración & dosificación , Poliinos/química , Poliinos/farmacología , Poliinos/uso terapéuticoRESUMEN
A new actinomycete strain designated MITKK-103 was isolated from the soil of a flowerpot using a humic acid agar medium. The newly isolated strain was able to produce a large amount of actinomycin X2 even under nonoptimized growing conditions and serves as a promising source of this antibiotic. Actinomycin X2 has higher cytotoxicity toward cultured human leukemia (HL-60) cells than does actinomycin D, and it induces cell death via apoptosis. A nearly complete 16S ribosomal DNA (rDNA) sequence from the isolate was determined and found to have high identity (98.5-100%) with Streptomyces galbus, Streptomyces griseofuscus, and Streptomyces padanus, indicating that MITKK-103 belongs to the genus Streptomyces. The isolate clustered with species belonging to the S. padanus clade in a 16S-rDNA-based phylogenetic tree and showed 75% overall homology to S. padanus ATCC 25646 in DNA-DNA relatedness analysis. Although the growth of the isolate was somewhat different from the three species mentioned, the strain MITKK-103 most closely resembles S. padanus on the basis of the morphological and phenotypic characteristics, phylogenetic analysis, and genotypic data. As such, this is the first report of a strain of S. padanus capable of producing actinomycins.
Asunto(s)
Dactinomicina/análogos & derivados , Microbiología del Suelo , Streptomyces/metabolismo , Técnicas de Tipificación Bacteriana , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Dactinomicina/biosíntesis , Dactinomicina/toxicidad , Células HL-60 , Humanos , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Filogenia , Pigmentos Biológicos/biosíntesis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido Nucleico , Streptomyces/clasificación , Streptomyces/aislamiento & purificación , Streptomyces/ultraestructuraRESUMEN
The human aging diseases Werner and Bloom syndromes are a result of mutation of the WRN and BLM genes, respectively. The SGS1 gene of Saccharomyces cerevisiae is homologous to the human WRN and BLM genes of the RecQ DNA helicase family. Deletion of SGS1 results in accelerated yeast aging and a reduction in life span as well as cell cycle arrest. We demonstrate that SGS1 deletion, DNA damage, and stress show similar transcriptional responses in yeast. Our comparative analysis of the genome-wide expression response of SGS1 deletion, stress and DNA damage indicates parallel transcriptional responses to cellular insult and aging in yeast.
Asunto(s)
Envejecimiento/fisiología , Daño del ADN/fisiología , ADN Helicasas/genética , Saccharomyces cerevisiae/fisiología , Eliminación de Gen , Regulación Fúngica de la Expresión Génica , Presión Osmótica , ARN Mensajero/metabolismo , RecQ Helicasas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae , Transcripción Genética/fisiologíaRESUMEN
Taxol (NSC-125973) is a poorly soluble plant product that exhibits excellent antimitotic properties. This study involves the development of a new formulation for taxol. The stability of taxol in a 50% triacetin emulsion as well as possible methods of intravenous administration of this dosage form was examined. A stable emulsion was found at taxol concentrations of 10 and 15 mg/ml of emulsion. The 50% triacetin emulsion showed an intravenous LD50 of 1.2 ml/kg in Swiss-Webster mice. The 10 mg/ml taxol formulation was demonstrated to be stable upon addition to 5% dextrose iv fluids provided that small packing systems were used. The taxol-triacetin emulsion can also be intravenously injected at various rates, and it may prove to be a useful formulation for taxol.