Recebido em 12/12/01; aceito em 5/11/02 SCREENING FOR ACETYLCHOLINESTERASE INHIBITORS FROM PLANTS TO TREAT ALZHEIMER'S DISEASE. Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognite impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activities. These symptons of AD have been successfully treated with acetylcholinesterase (AchE) inhibitors (eg. galanthamine). There still is great interest in finding better AchE inhibitors. We use Ellmann's microplate assay and silica gel thin-layer chromatography (TLC) to screen natural products from plants as new sources of AchE inhibitors.Keywords: Alzheimer disease; plants; cholinesterase inhibitors. INTRODUÇÃONa última década, a maneira de se pesquisarem novos compostos biologicamente ativos sofreu grandes mudanças, principalmente devido aos avanços tecnológicos. A indústria farmacêutica tem um papel importante no desenvolvimento de novos métodos, os quais podem propiciar, de forma mais rápida, o surgimento de novos medicamentos no mercado 1 . Um dos mais importantes fatores para o sucesso no descobrimento de um fármaco novo é a diversidade química dos compostos a serem selecionados, cujas fontes podem ser: compostos sintéticos, produtos naturais ou química combinatória. Entre estas possibilidades, os produtos naturais são considerados como uma das maiores fontes de diversidade química 2 . A natureza é uma fonte de inestimável riqueza de novos medicamentos. Nos EUA e Inglaterra, aproximadamente 25% dos compostos ativos, nas prescrições atuais, foram identificados em plantas superiores 3 . A avaliação biológica 1 foi uma das mais significantes mudanças na área de produtos naturais nos últimos anos. O entendimento dos mecanismos da doença, acompanhado do aumento de testes com receptores e enzimas disponíveis, permitiram o desenvolvimento de sistemas eficientes e rápidos de bioensaios. Dessa forma, um bom sistema permite selecionar milhares de amostras em poucos dias 1,4 . A modernização dos ensaios permitiu a utilização de enzimas, receptores, DNA, entre outros alvos, para avaliação rápida de grandes quantidades de amostras. Dentre os bioensaios rápidos e sensí-veis, a utilização da enzima acetilcolinesterase é uma alternativa para a detecção e seleção de amostras com ação anticolinesterase.Entre os indivíduos idosos, ressaltam-se as anormalidades decorrentes da disfunção do sistema nervoso, como deficiências relativas à memória, à capacidade intelectual, à coordenação motora, ao equilíbrio, à postura, etc.A demência, embora possa ocorrer nas idades jovens por enfermidades cerebrais variadas, está ligada ao fenômeno de envelhecimento cerebral, acometendo indivíduos com idade superior a 65 anos. Admite-se que 10 a 15% destes indivíduos apresentam alguma forma de demência e, deste grupo, 50 a 60% sofrem de uma doença degenerativa de causa não totalmente conhecida denominada doença de Alzheimer 5-8 . A doença de Alzheimer está associada ...
Descriptions of the use of natural products in traditional medicine have served as starting points for new therapeutics. The details of the traditional use of these organisms can provide important information for future drug discovery and development efforts. Recent technologic advances provide the framework to leverage ethnopharmacologic data in the drug discovery process. Information on the traditional harvest, preparation, storage, and administration of the organisms, and the natural products they contain, provides valuable details regarding characteristics of the active compounds. Importantly, researchers can now rapidly analyze and identify the multiple, and often synergistic, compounds contained in these natural products. Although we are entering the acme of ethnopharmacology, where information regarding the traditional use of organisms can provide valuable natural product leads and accelerate the identification of new therapeutics, this ethnopharmacologic resource is threatened by the loss of traditional medicine knowledge and extinction of organisms.
The growth of Tabernaemontana pachysiphon (Apocynaceae) plants and the alkaloid content of leaves were investigated in the greenhouse at three levels of nutrient supply under two contrasting water and light regimes. We determined height increment, above-ground biomass production, leaf size, specific leaf weight and the content of the alkaloids apparicine, A2, isovoacangine, tubotaiwine and tubotaiwine-N-oxide. The effects of major controlling factors such as light, water and nutrient supply could be directly correlated with growth and were largely independent of each other. In contrast, leaf-alkaloid contents were influenced by interdependencies among the main factors and individually affected in a synergistic or antagonistic manner which deviated from the effects on growth. The following general trends could be identified with respect to the quantitatively predominant alkaloids apparicine, tubotaiwine and isovoacangine. Increasing nutrient supply had a positive effect on both growth and alkaloid content. Drought increased alkaloid content, but retarded growth. High light intensity lowered alkaloid content but promoted growth. We investigated the relationship between primary production and the production of secondary metabolites with respect to relative and total alkaloid content as well as in relation to the leaves' nitrogen status. Our results showed that under conditions of low nutrient supply, higher proportions of leaf nitrogen were allocated to alkaloids than at moderate or high nutrient supply. Under conditions of drought and low light, all plants allocated almost equal proportions of leaf nitrogen to alkaloids, regardless of fertiliser. Total alkaloid content per plant, however, increased with fertilisation. With respect to the N-allocation strategy, we found no indication of a trade-off between primary production and the production of secondary metabolites in this species. Rather, our results are in accordance with the carbon nutrient balance hypothesis.
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