Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer's Disease Therapy (original) (raw)
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Plant-derived acetylcholinesterase inhibitory alkaloids for the treatment of Alzheimer's disease
Botanics: Targets and Therapy, 2013
The inhibition of acetylcholinesterase (AChE) has been one of the most used strategies for the treatment of Alzheimer's disease (AD). The AChE inhibitors (AChE-I) produce not only short-term symptomatic effects, but can also play a role in other pathological mechanisms of the disease (eg, formation of amyloid-β plaques), which has renewed interest in the discovery of such inhibitors. Four of the five currently prescribed treatments for AD are AChE-I. Natural alkaloids such as galantamine or alkaloid-related synthetic compounds (such as rivastigmine) are considered beneficial for patients with mild-to-moderate AD. However, there is a need for the discovery of more effective compounds and for this reason, plants can still be a potential source of new AChE-I. Findings and advances in knowledge about natural alkaloids as potential new drugs acting as AChE-I will be summarized in this paper.
Current Medicinal Chemistry, 2013
The leading Alzheimer's disease (AD) therapeutics to date involves inhibitors of acetylcholinesterase (AChE), which should, in principle, elevate cholinergic signaling and limit inflammation. In spite of the effectiveness in 20%-30% of AD patients, more attention has been paid to find new anti-AChE agents from medicinal plants. Galanthamine, contained in the bulbs and flowers of Galanthus and related genera like Narcissus, represents a good example. The aim of this study is to review the role of possible AChE inhibitors (AChEI) present in plants traditionally used in European medicine for improving memory. Starting from Galanthamine, properties of Melissa species, Salvia officinalis, Arnica chamissonis and Ruta graveolens are discussed to point to the role of these plants as potential sources for the development of therapeutic agents for AD.
South African Journal of Botany, 2018
The review focuses on acetylcholinesterase (AChE) inhibition of extracts and compounds from southern African plants. We provide a detailed inventory of southern African plants used in the treatment of central nervous system (CNS) and memory-related disorders that are potential candidates for novel AChE inhibitors. This was achieved through a detailed literature search using web-based database searches including Google Scholar, Scopus and Web of Science (WoS) as well as ethnobotanical literature on southern African medicinal plants. Bibliometric analysis was performed on the data mined from WoS. In addition, we reviewed the methods used to determine AChE activity and highlighted the success and potential of alkaloids from the Amaryllidaceae. Our findings revealed about 200 southern African medicinal plants that are used for CNS and memory-related disorders. Approximately, 65 southern African plants have been evaluated for AChE inhibitory activity even though the majority of these plants do not have an ethnobotanical basis for such evaluation. Several extracts (e.g. Ammocharis coranica (KerGawl.) Herb., Lannea schweinfurthii Engl, Scadoxus puniceus (L.) Friis & Nordal, Xysmalobium undulatum (L.) W.T.Aiton.) have been found to demonstrate noteworthy (IC 50 ≤ 1 μg/ml) AChE inhibitory activity. Moreover, 30 compounds have been isolated in an attempt to discover AChE inhibitors from southern African plants. The most active (IC 50 ≤ 12 μM) compounds were isolated from Crinum moorei Hook. f., Scadoxus puniceus and Acacia nilotica (L.) Willd. ex Del. subspecies kraussiana (Benth.). Thus far, very few South African studies have looked at the ecological and environmental impact of both naturally occurring and applied AChE inhibitors (e.g. organophosphate and carbamate insecticides) and no studies have considered medical applications other than in Alzheimer's disease (AD) therapy. Furthermore, most of these studies have mainly used an in vitro approach directed at developing treatments of age-related dementia such as AD, despite the decline in pharmaceutical interest of AChE inhibitors in the treatment of AD. It is also apparent that no further steps are taken towards the investigation of in vivo studies and clinical trials. In addition to these existing gaps, the pharmacodynamic and pharmacokinetic studies also need to be adequately addressed in order to generate more coordinated and focused research.
New Anti-Alzheimer Drugs from Biodiversity: The Role of the Natural Acetylcholinesterase Inhibitors
Mini-reviews in Medicinal Chemistry, 2005
Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays, drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD, and natural products have played an important alternative role in the research for new acetylcholinesterase inhibitors, as exemplified through the discovery of galantamine. This profile conducts us to give in this paper an overview relating the several classes of natural products with anti-cholinesterasic activity as potential templates to the design of new selective and powerful anti-Alzheimer drugs.
Molecules, 2016
Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer's Disease (AD). In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM) plants were tested for their in vitro anti-acetylcholinesterase activity based on Ellman's colorimetric assay. All three extracts of Berberis bealei (formerly Mahonia bealei), Coptis chinensis and Phellodendron chinense, which contain numerous isoquinoline alkaloids, substantially inhibited AChE. The methanol and aqueous extracts of Coptis chinensis showed IC 50 values of 0.031 µg/mL and 2.5 µg/mL, therefore having an up to 100-fold stronger AChE inhibitory activity than the already known AChE inhibitor galantamine (IC 50 = 4.33 µg/mL). Combinations of individual alkaloids berberine, coptisine and palmatine resulted in a synergistic enhancement of ACh inhibition. Therefore, the mode of AChE inhibition of crude extracts of Coptis chinensis, Berberis bealei and Phellodendron chinense is probably due to of this synergism of isoquinoline alkaloids. All extracts were also tested for their cytotoxicity in COS7 cells and none of the most active extracts was cytotoxic at the concentrations which inhibit AChE. Based on these results it can be stated that some TCM plants inhibit AChE via synergistic interaction of their secondary metabolites. The possibility to isolate pure lead compounds from the crude extracts or to administer these as nutraceuticals or as cheap alternative to drugs in third world countries make TCM plants a versatile source of natural inhibitors of AChE.
Acetylcholinesterase Inhibitors of Natural Origin
The endogenous neurotransmitter acetylcholine (ACh), found in vertebrates, stimulates cholinergic (muscarinic and nicotinic) receptors to mediate cholinergic neuronal transmission. ACh has a short half-life, as it is rapidly hydrolysed in the neuronal synaptic cleft by the enzyme acetylcholinesterase (AChE). Modulation of cholinergic function has been recognised as a therapeutic target in some disease states and one approach to achieve this is to prolong the action of ACh through the use of AChE inhibitors. Consequently, AChE inhibitors have been investigated for a number of therapeutic applications including glaucoma, myasthenia gravis, anti-muscarinic poisoning and dementia. Many inhibitors of AChE have been derived from natural sources, with alkaloids generally being the most potent, although other compounds including some terpenoids have also been shown to inhibit AChE. It is particularly interesting that of the four drugs currently licensed in Europe to alleviate cognitive symptoms in Alzheimer's disease, two (galantamine and rivastigmine) are derived from natural sources. Natural products continue to be investigated for anti-AChE activity to identify compounds that may have therapeutic potential, or that provide templates for the development of new drugs, with a particular focus on the alleviation of cognitive disorders. Many plants reputed to enhance cognitive function in a variety of traditional practices of medicine have been investigated to determine any pharmacological basis for their historical uses, and some of the extracts from these plants have shown promising AChE inhibitory effects, although for some plants the active compounds are yet to be elucidated. There are a number of other plants that are not associated with a traditional use related to cognitive disorders but their extracts have also been shown to inhibit AChE. Some of those plant extracts and compounds of natural origin that have shown inhibitory activity against AChE, and their therapeutic relevance, are discussed.
European Journal of Medicinal Chemistry, 1992
The study was carried out to identify the compound responsible for hypolipidemic and hypoglycemic effects of Cajanus cajan (redgram). The methanol extract of redgram seeds were fractionated into petroleum ether, chloroform, and methanol. The methanol fraction significantly decreased fasting blood glucose, and lipid profiles (p<0.001) on streptozotocin-induced mice compared to control. The methanol fraction was then subjected to chromatographic analysis and a compound (CCA1) has been isolated. The structure of the compound is considered to be substituted cyclopentene with glucose by analysis its 1 H and 13 C-NMR data. Biological studies of the isolated compound possessed prominent hypolipidemic activity. Although a number of hypoglycemic compounds are reported, yet not any hypolipidemic compound from redgram. The compound CCA1 seems to be the first report on hypolipidemic activity from methanol extract of redgram.
Natural products inhibitors of the enzyme acetylcholinesterase
Revista Brasileira de …, 2006
Alzheimer's disease (AD) is a progressive, neurodegenerative pathology that primarily affects the elderly population, and is estimated to account for 50-60% of dementia cases in persons over 65 years of age. The main symptoms associated with AD involve cognitive dysfunction, primarily memory loss. Other features associated with the later stages of AD include language deficits, depression, behavioural problems including agitation, mood disturbances and psychosis. One of the most promising approaches for treating this disease is to enhance the acetylcholine level in the brain using acetylcholinesterase (AChE) inhibitors. The present work reviews the literature on plants and plant-derived compounds inhibitors of enzyme acetylcholinesterase. The review refers to 309 plant extracts and 260 compounds isolated from plants, which are classified in appropriate chemical groups and model tested, and cites their activity. For this purpose 175 references were consulted.
Medicinal plants with acetylcholinesterase inhibitory activity
Reviews in the Neurosciences, 2018
Alzheimer’s disease, a progressive neurodegenerative disease, is characterised by hypofunction of acetylcholine (ACh) neurotransmitter in the distinct region of brain. Acetylcholinesterase (AChE) is an enzyme that metabolises the ACh at synaptic cleft resulting in Alzheimer’s disease. Medicinal plants have been used to treat numerous ailments and improve human health from ancient time. A traditional system of medicine is long recognised for its effective management of neurological disorders. The present review confers the scope of some common medicinal plants with a special focus on AChE-mediated central nervous system complications especially Alzheimer’s disease. Literature suggests that medicinal plants reduce neuronal dysfunctions by reducing AChE activity in different brain regions. In some instances, activation of AChE activity by medicinal plants also showed therapeutic potential. In conclusion, medicinal plants have a wide scope and possess therapeutic potential to efficientl...
Evaluation of Bioactive Compounds as Acetylcholinesterase Inhibitors from Medicinal Plants
Evidence-Based Validation of Herbal Medicine, 2015
As total life expectancy increases, the prevalence of age-related diseases such as Alzheimer's is also increasing. Many hypotheses about Alzheimer's disease have been developed, including cholinergic neuron damage. Acetylcholine is a major neurotransmitter in the brain and cholinergic deficits leads to cognitive dysfunction and decline. Despite decades of research and advances in our understanding of its aetiology and pathogenesis, current pharmacotherapeutic options for AD are still very limited and represent an area of need that is currently unmet. In abnormal activation of AChE, acetylcholine will degrade rapidly, especially in the brain and this is associated with Alzheimer's disease (AD). It has been shown that theraphy with essential oils from medicinal plants can improve cognitive performance in Alzheimer's disease patients. Eugenol from these essential oils is reported to inhibit acetylcholinesterase, both in vitro and in vivo. This paper is set to Determine inhibitory/stimulatory effect of tested extracts on acetylcholine esterase (AChE) activity. The sampled out plant extracts include Thymus vulgaris, Berberis vulgaris and Calluna vulgaris with which inhibition or activation by different chemical catalysts is performed to establish their effects in the tested natural extracts. Experimental design is used where the reagents are determined and chemical reactions performed in the procedures as outlined in the methodology section. The results of the cholinergic/ anticholinergic effect of tested natural extracts are then recorded. This study reflects that most of the extracts inhibited AChE activity with berberis vulgaris showing highest inhibitory effect.