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BACKGROUND AND AIM: In Mexican traditional medicine, Montanoa tomentosa (Mt) has been used as a remedy for reproductive impairments and mood swings. In pre-clinical research, both the extract and some of its active metabolites have produced oxytocinergic-like effects on female reproductive organs; however, there are no detailed studies of its effects on mood swing and brain structures. The aim of this study, was to analyze the behavioral effects of acute administration of a Mt infusion on male rats, during the Open Field (OFT) and Forced Swim (FST) Tests, and their association with the activation of oxytocin (OXT) cells, indicated by Fos protein (Fos/OXT) in the paraventricular (PVN) and supraoptic nuclei (SON). EXPERIMENTAL PROCEDURE: 52 adult male Wistar rats were assigned to two conditions; with FST (n = 8), or without (n = 5). Each integrated condition included four groups [Control, Vehicle, Fluoxetine (Flx; 10 mg/kg), and Mt (50 mg/kg), p.o.]. RESULTS AND CONCLUSION: Mt and Flx treatment produced an anti-despair-like effect on the FST, but no significant changes in locomotor activity. Also, the Mt infusion -but not Flx-significantly increased the number of Fos/OXT cells in the PVN and SON, regardless of the condition, compared to the control and vehicle groups. These results show that Mt, but not Flx, produces an anti-despair-like effect that could be associated with the activation of OXT cells in PVN and SON. This study thus contributes to our knowledge of the pharmacological activity of Mt infusions, which could be a natural antidepressant agent with future clinical relevance.

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The circadian clock is regulated at the molecular level by feedback circuits of a group of genes known as "clock genes", which establish a mechanism that controls circadian cellular physiology to maintain the balance between cell proliferation, response to DNA damage and apoptosis. Alterations in the expression of clock genes due to genetic or epigenetic mechanisms have been associated with multiple diseases including cancer. Even some clock genes such as the Per1, Per2, Bmal1 genes have been proposed as tumor suppressor genes, with a relevant role during carcinogenesis. At the molecular level, multiple mechanisms of molecular control have been described to link circadian transcription, cell cycle control, and tumorigenesis. In addition, recent findings describe an epigenetic control of circadian transcription, at the level of DNA methylation as well as in the modifications of histones. However, the link between the circadian epigenome and cancer remains unclear. In this article, we review the evidence that suggests a relationship between alterations in the expression of clock genes, with the development of cancer, from the epigenetic landscape.

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OBJECTIVE: Argemone mexicana is a Papaveracea plant; some reports have shown their antibacterial, anti-cancer, sedative and probably anti-anxiety properties. From their aerial parts, flavonoids and alkaloids have been isolated, which are intrinsically related to some actions on the central nervous system. The aim of this study was to evaluate the anxiolytic-like effects of the plant, using its ethanolic extract and alkaloid-enriched extract obtained from fresh leaves. MATERIAL AND METHODS: Phytochemical screening was carried out together with evaluation of antioxidant capacity and the enrichment of alkaloids present in the extract. Subsequently, 100 and 200 mg/kg doses of ethanolic extract and alkaloid-enriched extract (200 µg/kg) were intraperitoneally administered to female Wistar rats, which were exposed to elevated plus maze (EPM) test. Picrotoxin (1 mg/kg), a non-competitive gamma-aminobutyric acid A (GABAA) chloride channel antagonist, was used in experimental procedures to evaluate if this receptor is involved in the anxiolytic-like effects of A. mexicana. To discard motor effects associated with the treatments, the rats were evaluated by the locomotor activity test. RESULTS: Only the ethanolic extract at 200 mg/kg and alkaloid-enriched extract (200 µg/kg) produced anxiolytic-like effects similarly to diazepam 2 mg/kg on EPM test, without affecting locomotor activity. Meanwhile, the administration of picrotoxin blocked anti-anxiety effect of alkaloid-enriched extract of the plant. CONCLUSION: These results showed that A. mexicana is a potential anxiolytic agent and we suggest that this effect is mediated by the GABAA receptor. These effects are related to the presence of alkaloids.

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The aim of this study was to identify compounds that possess anticonvulsant activity by using a pentylenetetrazol (PTZ)-induced seizure model. Theoretical studies of a set of ligands, explored the binding affinities of the ligands for the GABA(A) receptor (GABA(A)R), including some benzodiazepines. The ligands satisfy the Lipinski rules and contain a pharmacophore core that has been previously reported to be a GABA(A)R activator. To select the ligands with the best physicochemical properties, all of the compounds were analyzed by quantum mechanics and the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital were determined. Docking calculations between the ligands and the GABA(A)R were used to identify the complexes with the highest Gibbs binding energies. The identified compound D1 (dibenzo(b,f)(1,4)diazocine-6,11(5H,12H)-dione) was synthesized, experimentally tested, and the GABA(A)R-D1 complex was submitted to 12-ns-long molecular dynamics (MD) simulations to corroborate the binding conformation obtained by docking techniques. MD simulations were also used to analyze the decomposition of the Gibbs binding energy of the residues involved in the stabilization of the complex. To validate our theoretical results, molecular docking and MD simulations were also performed for three reference compounds that are currently in commercial use: clonazepam (CLZ), zolpidem and eszopiclone. The theoretical results show that the GABA(A)R-D1, and GABA(A)R-CLZ complexes bind to the benzodiazepine binding site, share a similar map of binding residues, and have similar Gibbs binding energies and entropic components. Experimental studies using a PTZ-induced seizure model showed that D1 possesses similar activity to CLZ, which corroborates the predicted binding free energy identified by theoretical calculations.

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In Mexico, Raphanus sativus L. var. niger (black radish) has uses for the treatment of gallstones and for decreasing lipids serum levels. We evaluate the effect of juice squeezed from black radish root in cholesterol gallstones and serum lipids of mice. The toxicity of juice was analyzed according to the OECD guidelines. We used female C57BL/6 mice fed with a lithogenic diet. We performed histopathological studies of gallbladder and liver, and measured concentrations of cholesterol, HDL cholesterol and triglycerides. The juice can be considered bioactive and non-toxic; the lithogenic diet significantly induced cholesterol gallstones; increased cholesterol and triglycerides levels, and decreased HDL levels; gallbladder wall thickness increased markedly, showing epithelial hyperplasia and increased liver weight. After treatment with juice for 6 days, cholesterol gallstones were eradicated significantly in the gallbladder of mice; cholesterol and triglycerides levels decreased too, and there was also an increase in levels of HDL (P < 0.05). Gallbladder tissue continued to show epithelial hyperplasia and granulocyte infiltration; liver tissue showed vacuolar degeneration. The juice of black radish root has properties for treatment of cholesterol gallstones and for decreasing serum lipids levels; therefore, we confirm in a preclinical study the utility that people give it in traditional medicine.

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La epilepsia es una afección crónica producida por diferentes etiologías, caracterizada por la repetición de crisis debidas a una descarga excesiva de las neuronas cerebrales asociadas a síntomas clínicos o paraclínicos. Se debe a una despolarización rápida, en la membrana, de iones en una población de neuronas susceptibles, es decir, un cambio repentino en la carga intracelular negativa a positiva. Las causas más conocidas son: alteraciones genéticas, anoxia perinatal, traumatismos, tumores, malformaciones congénitas, alteraciones metabólicas, intoxicaciones farmacológicas, infecciones del sistema nervioso. Una crisis epiléptica es la aparición transitoria de signos y síntomas anormales causados por la actividad neuronal excesiva, mientras que la epilepsia se caracteriza por una permanente predisposición a generar crisis. En la despolarización de la membrana neuronal, los iones calcio desempeñan un papel importante debido a que son mensajeros intracelulares que regulan funciones como: liberación de neurotransmisores, neurosecreción, excitación neuronal, supervivencia de neuronas y regulación de expresión de genes. El ingreso de calcio a través de la membrana plasmática representa una forma para controlar el nivel intracelular de calcio. Se conoce poco sobre el mecanismo de entrada del calcio a la neurona pero un progreso notable representa la comprensión de la estructura, función y regulación de los canales de calcio dependientes de voltaje.

Epilepsy is defined as a chronic condition produced by different etiologies, characterized by the repetition of crises due to an excessive discharge of the cerebral neurons assoclated wlth cllnlcal symptoms. It responds to a fast ion depolarization in a population of abnormal neurons. Causes of epilepsy are: genetíc alteratíons, perínatal anoxía, traumatísms, tumors, congenital malformations, metabolic alterations, drug poisonings, and infections of the nervous system. Epileptic selzure Is the transitory occurrence of signs and abnormal symptoms caused by excessive or synchronous neurona! activity whereas, epilepsy Is characterized by a permaneni predisposition to genérate seizures. During depolarization of neurona! membrane, calcium ions play an important role because they are intracellular messengers that regúlate functions llke: neurotransmltter reléase, neurosecretlon, neuronal excltatlon, neuron survlval and gene expresslon regulatlon . The Influx of calcium through the plasmatlc membrane represents a way to control Intracellular calcium level. The mechanlsm of the entrance of calcium to the neuron Is llttle known, but understandlng the structure, functlon and regulatlon of voltage-gated calcium channels Is of remarkable progress.