Composición química y actividad AChE-BuChE del aceite esencial de palo santo Bursera graveolens (Kunth) Triana & Planch de Jipijapa, Ecuador / Chemical composition and AChE-BuChE activities of the essential oil of palo santo Bursera graveolens (Kunth) Tr iana & Planch from Jipijapa, Ecuador

Abstract: This article describes the chemical composition, physical properties and acetylcholinesterase (A ChE) and butyrylcholinesterase (BuChE) activity of stem - distilled essential oil (E O ) from Bursera graveolens wood chips, Burseraceae. The plant material was acquired in Quimis (Bosque de Sancán), city of Jipijapa in the province of Manabí, coastal region o f Ecuador. Thirty - six components were identified by CG - MS, which represented 98.54% of the volatile oil. The main components were limonene (68.52%) and mentofuran (20.37%). The hydrocarbon monoterpenes constituted the most abundant fractions. The average y ield of the E O was 1.26%. Regarding the physical properties of E O , the following values were obtained: relative density (1,029 g/mL), refractive index (1,477) and specific rotation (+4,567). The E O presented IC 50 inhibition values of 47.2 and 51.9 µg/mL fo r the enzymes AChE and BuChE, respectively.

Resumen: Este artículo describe la composición química, propiedades físicas y actividad acetilcolinesterasa (AChE) y butirilcolinesterasa (BuChE) del aceite esencial (AE) destilado a vapor de astillas de madera de Bursera graveolens , Burseraceae. La materia vegetal fue adquirida en Quimis (Bosque de Sancán), ciudad de Jipijapa en la provincia de Manabí, región costera d e Ecuador. Treinta y seis componentes fueron identificados por CG - MS, que representaron al 98.54 % del aceite volátil. Los componentes principales fueron limoneno (68.52%) y mentofurano (20.37%). Los monoterpenos hidrocarburos constituyeron las fracciones m ás abundantes. El rendimiento medio del AE fue de 1.26%. Con respecto a las propiedades físicas del AE se obtuvo los siguientes valores, densidad relativa (1.029 g/mL), índice de refracción (1.477) y rotación específica (+4.567). El AE presentó valores de inhibición IC 50 de 47.2 y 51.9 µg/mL para las enzimas AChE y BuChE, respectivamente.

Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Exposição ambiental/ocupacional aos agrotóxicos em gestantes residentes em um município rural / Environmental/occupational exposure to pesticides of pregnant women living in a countryside municipality / Exposición ambiental/ocupacional a los agrotóxicos en gestantes residentes en un municipio rural

Objective: The study's goal has been to analyze if environmental or occupational exposure to pesticides can produce changes in pregnant women living in a countryside municipality. Methods: The participants of this study were twenty-three pregnant women, who both answered a questionnaire and donated biological material in order to perform Micronucleus (MN) Tests in lymphocytes, oral epithelial cells, and also for measuring the enzyme activity of erythrocyte acetylcholinesterase. Results: Considering the total analyzed samples, the following was found: an average of 8 ± 2.92 MN/1000 oral epithelial cells from urban participants; an average of 6.82 ± 3.43 MN/1000 oral epithelial cells from rural participants; and 100% of the microscope slides contained cells with two MN, which shows high intensity lesions to the DNA. There was found a high frequency of spontaneous abortions (34.8%), greater than in Brazil. Conclusion: The exposure of pregnant women living in a countryside municipality to pesticides may increase the rate of spontaneous abortions, as well as the chances of mutagenic effects

Objetivo: Analisar se a exposição ambiental ou ocupacional aos agrotóxicos causa alterações em gestantes residentes em um município rural. Métodos: Compuseram a amostra 23 gestantes, que responderam a um questionário e doaram amostras biológicas para a realização dos testes de micronúcleos (MN) em linfócitos, em células do epitélio oral, e para a dosagem da atividade da enzima acetilcolinesterase eritrocitária. Resultados: Obteve-se uma média de 8 ± 2,92 MN/1000 células do epitélio oral analisadas em amostras de participantes da zona urbana, 6,82 ± 3,43 MN/1000 de participantes da zona rural, e 100% das lâminas continham células com dois MN, o que demonstra lesões ao DNA de maior intensidade. Encontrou-se uma frequência elevada de casos de abortos espontâneos (34,8%), superior à encontrada no Brasil. Conclusão: A exposição de gestantes residentes em um município rural aos agrotóxicos eleva a taxa de abortos espontâneos, bem como as chances de ocorrência de efeitos mutagênicos

Objetivo: Analizar si la exposición ambiental o ocupacional a los agrotóxicos causa cambios en gestantes residentes en un municipio rural. Métodos: Compusieron la muestra 23 gestantes, que respondieron a un cuestionario y donaron muestras biológicas para la realización de las pruebas de micronúcleos (MN) en linfocitos, en células del epitelio oral, y para la dosificación de la actividad de la enzima acetilcolinesterasa eritrocitaria. Resultados: Se obtuvieron una media de 8 ± 2,92 MN / 1000 células del epitelio oral analizadas en muestras de participantes de la zona urbana, 6,82 ± 3,43 MN / 1000 de participantes de la zona rural, y el 100% de las láminas contenían células con dos MN, lo que demuestra lesiones al ADN de mayor intensidad. Se encontró una frecuencia elevada de casos de abortos espontáneos (34,8%), superior a la encontrada en Brasil. Conclusión: La exposición de gestantes residentes en un municipio rural a los agrotóxicos eleva la tasa de abortos espontáneos, así como las posibilidades de ocurrencia de efectos mutagênicos

Avaliação "in vitro" do efeito da infusão de Cunila microcephala Benth sobre a atividade da enzima acetilcolinesterase e biomarcadores de estresse oxidativo em eritrócitos de agricultores / Effect of the Cunila microcephala Benth infusion on the activity of Acetilcolinesterase enzyme and on the biomarkers of oxidative stress in farmers erythrocytes

RESUMO Tivemos como objetivo avaliar o efeito da infusão de Cunila microcephala Benth sobre a atividade da enzima acetilcolinesterase (AChE) e marcadores de estresse oxidativo em eritrócitos de agricultores. Foram utilizadas amostras provenientes de 16 trabalhadores rurais expostos a pesticidas agrícolas pelo período mínimo de 5 anos e um grupo controle constituído de 16 indivíduos não expostos a agrotóxicos. As hemácias dos agricultores e o grupo A foram expostos “in vitro” à solução salina (NaCl 0,9%). Os demais grupos foram expostos à infusão de poejo nas concentrações de 0; 5; 10; 25 e 50 g/L (Grupos B; C; D e E, respectivamente). Em seguida, foram realizadas as determinações da atividade da AChE e dos níveis de substâncias reativas ao ácido tiobarbitúrico (TBARS), proteínas carboniladas (PCs) e glutationa reduzida (GSH). Os resultados mostram que a infusão de poejo 50g/L, aumenta a atividade da enzima AChE e os níveis de GSH. Contudo, os níveis de TBARS e PCs diminuíram após o tratamento com a infusão de poejo 25 e 50 g/L. A infusão de poejo, na concentração de 50 g/L, é capaz de reverter, “in vitro” a inibição da atividade da AChE que ocorre pela exposição a pesticidas, e ainda demonstra um importante potencial antioxidante, tendo em vista que diminuiu danos lipídicos e proteicos e ainda, estimulou a produção do principal antioxidante não enzimático endógeno.

ABSTRACT Evaluating the effect of infusion Cunila microcephala Benth on acetylcholinesterase activity (AChE) enzyme and on biomarkers of oxidative stress in farmers erythrocytes. We used samples from 16 rural workers exposed to pesticides for a minimum of five years, and a control group composed of 16 individuals not exposed to pesticides. The erythrocytes of farmers and from group A were exposed “in vitro” the saline solution (NaCl 0,9%). The other groups were exposed to the infusion of “poejo” at concentrations of 0; 5; 10; 25 and 50 g/L (Groups B, C, D and E, respectively). Then, it was realized the analitical determinations of AChE activity and TBARS, PCs and GSH levels. The results showed that “poejo” infusion 50g/L, increased the AChE activity and GSH levels. However, the TBARS e PCs levels decreased after the treatment with “poejo” infusion 25 e 50 g/L. The “poejo” infusion 50 g/L is able to revert “in vitro” the inhibition of AChE activity that occurs by exposure to pesticides and also demonstrates an important antioxidant potential, given that decreased lipid and protein damage and also it stimulated the production of the main non-enzymatic antioxidant endogenous.

Correlação entre as atividades antiradical, antiacetilcolinesterase e teor de fenóis totais de extratos de plantas medicinais de farmácias vivas / Correlation between the anti-radical, anti-acetylcholinesterase activities and phenolic content of some extracts of live herbal pharmacies in the Northeast of Brazil

O objetivo deste trabalho foi avaliar a correlação entre o conteúdo de fenóis de extratos de 18 plantas medicinais comuns nas Farmácias Vivas com a atividade sequestradora do radical livre DPPH e com a inibição da enzima acetilcolinesterase. Maiores conteúdos de fenóis totais foram encontrados nas plantas: Eugenia uniflora, Lippia alba, Lippia microphylla, Mentha x villosa, Ocimum gratissimum e Ocimum selloi. As espécies que apresentaram maior atividade antioxidante, semelhante a quercetina, foram: Spondias mombim, Malphigia glabra, L. alba e Croton zenhtneri,. As plantas Cecropia pachystachia, L. alba, L. microphylla, M. glabra, O. gratissimum e Plectranthus ornatus mostraram maiores halos de inibição da enzima acetilcolinesterase. Combinando as duas ações, as plantas mais ativas foram a M. glabra e a L. alba e somente a segunda correlaciona-se diretamente com o maior teor de fenóis totais. Através deste estudo, M. glabra e L. alba foram consideradas as plantas mais promissoras para estudos subsequentes a fim de encontrar novos compostos com ação potencial contra a doença de Alzheimer.

The purpose of this study was to evaluate the phenolic content of 18 medicinal plant extracts of "Live Pharmacies" and correlate them with their free radical scavenging activity and inhibition of the acetylcholinesterase enzyme. Higher amounts of phenolic compounds were found in the following plants: Eugenia uniflora, Lippia alba, Lippia microphylla, Mentha x villosa, Ocimum gatissimum, and Ocimum selloi. The species that showed higher anti-radical activity were Croton zenhtneri, Lippia alba, Malphigia glabra, and Spondias mombim, similar to quercetin. The plants Cecropia pachystachia, L. alba, L. microplylla, M. glabra, O. gratissimum, and Plectranthus ornatus showed larger inhibition zones of the acetylcholinesterase enzyme. By correlating the two actions L. alba and M. glabra are common as more active to both tests and only L. alba correlates directly with the phenolic content. Through this study, L. alba and M. glabra are considered the most promising plants for further studies to find new compounds with potential action against Alzheimer's disease.

Enfermedad de Alzheimer: Tratamientos actuales y futuros / Alzheimer's Disease: Current and Future Treatments

Unas 25 millones de personas padecen enfermedad de Alzheimer en el mundo, y probablemente en los práximos 20 años, se registrarán unos 70 millones de nuevos casos. Caracterizaada por una pérdida progresiva de la memoria, el déficit de la capacidad cognitiva es proporcional a la densidad de placas seniles, a la acumulación de la proteína beta amiloide, degeneraciones neuríticas y ovillos neurofibrilares, particularmente en el hipocampo y en la corteza cerebral. Este cuadro histopatológico se asocia a otro neuroquímico, caracterizado por una disminución de las enzimas colina acetiltransferasa y acetilcolinesterasa, y una menor densidad de los receptores colinérgicos muscarínicos y nicotínicos. Ello ha generado la teoría colinérgica del Alzheimer, que ha dado lugar a una aproximación racional al tratamiento de la enfermedad. Hoy disponemos de 3 anticolinesterásicos, galantamina, donepecilo y rivastigmina aprobados por FDA, que se recomiendan en EA leves y moderadas y de un antagonista no competitovo de los receptores NMDA memantina EA. El beneficio es modesto en relación a lo cogitivo y conductual. Se incluyen estudios sobre recomendaciones, farmacología, farmacognética, eficacia, tolerancia, características de los pacientes respondedores a los diferentes anticolinesterásicos, sus reemplazos el uso de comprimidos, parches, beneficiios, efectos adversos y de las nuevas terapéuticas que están en desarrollo como estanercept, NP12, resveratrol PBT2 y vacuna nasal, entre otras...

About 25 millions of individuals in the world suffer from Alzheimer's disease. The next 20 years shall probably register 70 millions of new cases. Characterized by a progressive loss of memory, cognitive deficit is proportional to the density of senile plaques, accumulation of beta amyloid, neuritic degeneration and neurofibrillary tangles, particularly in the hippocampus and cerebral cortex. This histopathological condition is associated with another neurochemical, chracterized by a decrease in choline acetyltransferase and acetylcholinesterase enzymes, and a lower density of muscrinic and nicotinic cholinergic receptors. This results in the cholinergic theory of Alzheimer's, which has led to a rational approach to treatment of disease. Today we have 3 anticholinesterase Galantamine, Donepzil and Rivastigmine approved by FDA recommended in mild to moderate AD and an uncompetitive antagonist of NMDA receptors Memantine is recommended in mild Alzheimer's disease for people who can not take ACE inhibitors, and severe AD The benefit is modest in realtion to the cognitive and behavioral. Studies are included on therapeutic recommendations, pharmacology, pharmacogenetic, efficiency, tolerance, characteristics of responders to different anticholinesterases, their relacements, the use of pills, patches, benefits, side effects and new therapeutic under development as Etanercept, NP12, PBT 2, Resveratrol, Nasal Vaccine, among others...