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Zajac D.,Polish Academy of Sciences | Stasinska A.,Polish Academy of Sciences | Delgado R.,Drug Research and Development Center | Pokorski M.,Polish Academy of Sciences
Advances in Experimental Medicine and Biology | Year: 2013

Mangiferin, the main active substance of the mango tree bark (Mangifera indica L.), is known for its use in natural medicine, not only as a health enhancing panacea or adjunct therapeutic, but also for brain functions improvement. In this context, we deemed it worthwhile to establish whether mangiferin could traverse into the brain after systemic administration; an essential piece of information for the rational use of a compound as a neurotherapeutic, remaining so far inconclusive regarding mangiferin. We addressed this issue by studying recoverability of mangiferin in membrane and cytosolic fractions of rat brain homogenates after its intraperitoneal administration in a dose of 300 mg/kg. We used three preparations of mangiferin of decreasing purity to find out whether its penetration to the brain could have to do with the possible presence of contaminants. The qualitative methods of thin-layered-chromatography and UV/VIS spectrophotometry were employed in this study. The results were clearly negative, as we failed to trace mangiferin in the brain fractions with either method, which makes it unlikely that the compound traverse the blood-brain barrier after being systemically administered. We conclude that it is improbable that mangiferin could act via direct interaction with central neural components, but rather has peripheral, target specific functions which could be secondarily reflected in brain metabolism. © 2013 Springer Science+Business Media Dordrecht.

Parraa A.L.,Drug Research and Development Center | Rodriguez J.C.G.,National Center for Laboratory Animal Breeding
Central Nervous System Agents in Medicinal Chemistry | Year: 2012

The most common cause of stroke is cerebral ischemia, where blood flow to the brain is interrupted due to a thrombus in a major cerebral artery. Currently, the only therapeutic approach available is thrombolysis. A more recent approach that has started to gain attention is neuroprotection, the ability to prevent neuronal death and enhance endogenous protective mechanisms. Several studies have shown the neuroprotective action of Erythropoietin (EPO). A potential problem in the use of EPO for neurodegenerative disorders is the undesirable erythropoietic side effects. In this context, investigations have been focused to develop derivatives of EPO lacking erythropoietic activity but retaining neuroprotective potential. Low sialic acid-containing EPO (Neuro EPO) is very similar to the one that occurs in the mammalian brain and is rapidly degraded by the liver. Similar neuroprotective effects had been observed with neuro EPO, original recombinant human EPO and EPO variants in ischemia models. Intranasal route could be safe and hematological side effects could be avoided. Neuro EPO that constitutes a new agent has retained the neuroprotective effects without stimulating the EPOR in the bone marrow and can therefore be used without increasing the hematocrit. This review gives a brief introduction to the no hematopoietic effects of EPO, the evidence of neuroprotective effect, the alternatives for obtaining an EPO derivate without hematological side effects and discusses the advantages of nasal administration of Neuro EPO for neuroprotective stroke treatment. © 2012 Bentham Science Publishers.

Pokorski M.,Polish Academy of Sciences | Pokorski M.,University of Opole | Rekawek A.,Polish Academy of Sciences | Zasada I.,Polish Academy of Sciences | And 2 more authors.
Advances in Experimental Medicine and Biology | Year: 2012

Reactive oxygen species favor the reductive state of iron. Antioxidation, by depleting biologically active ferrous iron, could then have a stabilizing effect, akin to hypoxia, on HIF-1α; the process which controls the genetic responses to hypoxia. However, the influence of antioxidation on the hypoxic ventilatory responses (HVR) is unclear. In this study we set out to determine the influence of mangiferin, a natural polyphenolic compound present in mango trees, with strong antioxidant and iron chelating properties, on the HVR. The study was performed in awake Wistar rats. Acute HVR to 12% and 8% FiO 2 before and 40 min after mangiferin (300 mg/kg, i.p.) pretreatment were recorded plethysmographically. We found that mangiferin significantly dampened the HVR over its course. To distinguish between the scavenging and chelating mechanisms of mangiferin we reinvestigated its effects on the HVR in a separate group of rats after chronic antecedent iron chelation with ciclopirox olamine (20 mg/kg daily for 1 week). The dampening effect on the HVR of mangiferin was preserved in the pre-chelated rats, which points to the preponderance of the antioxidant over chelating properties of mangiferin in its ventilatory effects. Although the exact determinants of mangiferin action remain unclear, the study suggests a role for oxidative signaling in the peripheral chemosensory processing of the HVR. The study also implies the possible clinical use of the antioxidant mangiferin in the regulation of lung ventilation. © Springer Science+Business Media Dordrecht 2012.

Piloto Ferrer J.,Drug Research and Development Center | Piloto Ferrer J.,University of Habana | Stoiber T.,Institute of Molecular Biotecnology | Vizoso Parra A.,Drug Research and Development Center | And 4 more authors.
Boletin Latinoamericano y del Caribe de Plantas Medicinales y Aromaticas | Year: 2011

The main objective of anti-carcinogenic chemotherapy is to stop uncontrolled cellular proliferation. This has prompted us to begin a systematic survey of new effective inhibitors with ability to react with cytoskeletal components and arrest living, dividing cells. Even for traditional populations herbs-consuming, encouraging the use of species with chemopreventive actions could be helpful as part of life expectancy improvement strategies. Herbal products have significantly lower costs, exhibit little or no toxicity during long-term oral administration and are relatively available at large scale. Current work involved the screening of 85 extracts from Cuban medicinal plants, selected on the basis of traditional use, ethnobotanics and pharmacological information (antiparasitic, antitumour, abortive, etc.). Antitubulinic activity in the hydroalcoholics extracts was evaluated by using a modified version of the conventional turbidity assay of tubulin assembly/ disassembly. The activity limits of the news isolated antitubulin agents were thoroughly investigated. According to the presented results, the extracts displaying the highest antitubulinic activity were Tamarindus indica L., Lawsonia inermes L and Xanthium strumarium L. © 2011 The Authors.

Lagarto A.,Drug Research and Development Center | Bueno V.,Drug Research and Development Center | Guerra I.,Drug Research and Development Center | Valdes O.,Drug Research and Development Center | And 2 more authors.
Experimental and Toxicologic Pathology | Year: 2011

We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000. mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000. mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low. © 2010 Elsevier GmbH.

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