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Unique Journal of Engineering and Advanced Sciences A REVIEW ON NATURAL MEMORY ENHANCERS (NOOTROPICS)
Abstract
Nootropics also referred to as smart drugs, memory enhancers, neuro enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that purportedly improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration. Nootropics are thought to work by altering the availability of the brain's supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brain's oxygen supply, or by stimulating nerve growth. Drugs considered cognitive enhancers include dietary products and supplements, racetams, stimulants, dopaminergics, cholinergics, GABA blockers, glutamate activators, serotonergics and hormones, etc. however not all are healthy or safe to use but they can still have mental benefits. The safest types of cognitive enhancers constist of herbal drugs and are available in supplement form, which mostly contain vitamins, fatty acids, antioxidants, amino acids, minerals, etc and other herbal ingredients. Vitamins are involved in brain development and in adult brain function. Omega-3 influences both communication between cells and cell function. Antioxidants help to retain the mental abilities longer, keep the brain younger and protect it from oxidative damage. Amino acids help to produce the catecholamines and create alertness. Hormones increase neurogenesis and improve both memory encoding and recall. Iron helps create hemoglobin, which transports oxygen to the brain. Creatinine protects ATP during transport. Lipoic acid improves oxygen usage and antioxidant recycling, improving memory and Germanium increases oxygen supply to the brain. Herbs and herbal products which have been found useful in improving cognitive ability include Bacopa monniera, Ginkgo biloba, Siberian ginseng, Rhodiola rosea, Brahmi rasayana, , Lycoris radiata, Sutherlandia frutescens, Mucuna pruriens, Butea frondosa, St John's Wort, Arecholine, Royl Jelly, Caffeine, Curcumin and so on. The mechanism of action is different for different drugs. These drugs are used primarily to treat people with cognitive difficulties as in Alzheimer's disease, Parkinson's disease and Attention-deficit hyperactivity disorder (ADHD).
... Środki nootropowe, zwane popularnie nootropami, stymulatorami pamięci/neuronów to produkty lecznicze, suplementy diety lub żywność funkcjonalna wspomagające poprawę funkcji poznawczych, a w szczególności pamięć, kreatywność i motywację działania. Nazwę swoją zawdzięczają rumuńskiemu chemikowi i psychologowi Corneliu E. Giurgea (odkrywcy właściwości piracetamu), który w 1972 r. utworzył to pojęcie, wykorzystując dwa greckie rzeczowniki noos (dopełniacz słowa nóus -rozum, intelekt) oraz trop, wyraz wywodzący się od rzeczownika trópos, a oznaczający zwrot, zmianę, odmianę, sposób [1,2]. ...
... ; zapobiegające uszkodzeniom komórek mózgowych oraz ich ochrona przed stresem oksydacyjnym [1,15]. ...
... Cholinergiczne nootropy obejmują: -prekursory acetylocholiny: ; cholinę -prekursor fosfatydylocholiny i acetylocholiny [1,18]; ; DMAE (2-dimetyloaminoetanol, N,N-dimetyloetanoloamina) -produkt pośredni w endogennej syntezie choliny [1,18]; ; meklofenoksat -połączenia DMAE z kwasem p-chlorofenoksyoctowym (pCPA) [1,18]; ; alpha-GPC (alfosceran choliny, α-glicerylofosforylcholina) -produkt dostarczający cholinę do mózgu, pokonujący barierę krew--mózg; stosowany w zaburzeniach pamięci, dezorientacji, zmniejszeniu motywacji oraz koncentracji, w zaburzeniach afektu i zachowania, niestabilności emocjonalnej, drażliwości oraz zaniku zainteresowania otoczeniem [31]; -kofaktory uczestniczące w syntezie acetylocholiny: ; acetylo-L-karnitynę -aminokwas, który bierze udział w procesach transacetylacji i jest donorem grupy acetylowej w reakcji powstawania acetylo-CoA [1,18]; ; witaminę B 5 (kwas pantotenowy) -kofaktor przemiany choliny w acetylocholinę [1,18]; -inhibitory acetylocholinoesterazy (ang. Acetylcholinesterase Inhibitor, AChEI) -blokujące enzym/y rozkładający/e acetylocholinę w szczelinie synaptycznej: ; donepezil -swoisty odwracalny inhibitor acetylocholinoesterazy (AChE) stosowany w chorobie Alzheimera w leczeniu objawowym łagodnej do umiarkowanie ciężkiej postaci otępienia [32]. ...
Nootropics also called smart drugs, memory enhancers, neuroenhancers, cognitive enhancers, are a chemically and pharmacologically heterogeneous group of medicines and active sub-stances that improve mental functions such as memory, intelligence, motivation, attention, and concentration. They are used to treat cognition deficits in patients suffering from dementia, schizophrenia, stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, and ADHD. According to the definition, which was proposed by a Romanian psychologist and chemist Corneliu E. Giurgea nootropics should be characterized by the ability to cross the blood-brain barrier, lack of typical pharmacological effects of psychotropic medicines, a small number of reported side effects, and extremely low toxicity. Their pharmacological activity depends on various mechanisms of action. They stimulate the metabolism of nerve cells and increase their resistance to hypoxia, regulate cerebral circulation, as well as exhibit anticoagu-lant/antiplatelet and neuroprotective properties. In addition, these compounds directly or indi-rectly increase the concentration of neurotransmitters essential for appropriate brain function-ing such as acetylcholine, dopamine, and glutamate. Therefore, procognitive medicines which increase cholinergic transmission are used in the symptomatic treatment of mild to moderate dementia associated with Alzheimer's disease. Collaterally to synthetic nootropics, there is also a group of natural plant substances that have proven the ability to improve brain function. They have a beneficial effect on cognitive functions such as learning ability, memory, concen-tration and exhibit neuroprotective action. Natural nootropics also slow down the aging pro-cesses, progressing with age and intensifying cognition deficits. But nowadays, medicines that help people with neurological and psychiatric conditions are used by healthy individuals as brain boosters because they increase concentration level, motivation, memory functions, and efficiency while reducing sleep time without feeling tired. Therefore they are willingly taken by students and people working in highly competitive industries. There is a number of natural and synthetic brain boosters available, but some of them exhibit a lot of side effects.
... Therefore, research of phytopharmaceuticals obtained from medicinal plants of traditional origin can be beneficial. 2 In consequence, the natural system of medicine is exploring the remarkable benefits from the herbs used in various aspects and one of the aspects include brain function such as improving memory, improving alertness, improving intelligence, improving mental performance etc. 27 The term nootropic was coined by Dr. Corneliu E. Giurgea in lexical analogy to "psychotropic", and comes from the Greek words for "mind" (noos) and "towards" (tropein). 1,28 They are also referred to as neuroenhancers, smart drugs, memory enhancers, cognitive enhancers, and intelligence enhancers and are used in cognition deficits commonly found in patients suffering from Alzheimer's disease (AD), schizophrenia, stroke, attention 3. protect the brain against various physical or chemical injuries (e.g. ...
... Nootropics are an extensive and structurally heterogeneous class of drugs, supplements, nutraceuticals, and functional foods that enhance one or more aspects of mental function. 27,29 Among the better known aspects (Figure 2) of mental and brain functions enhanced by nootropics reported in the literature are: a) attention, b) blood circulation, c) concentration, d) cognition, e) intelligence, f) learning, g) memory, h) motivation, and, i) working memory. 9,27,29,37 ...
... 27,29 Among the better known aspects (Figure 2) of mental and brain functions enhanced by nootropics reported in the literature are: a) attention, b) blood circulation, c) concentration, d) cognition, e) intelligence, f) learning, g) memory, h) motivation, and, i) working memory. 9,27,29,37 ...
... It is used as brain tonic by inculcating the whole herb of 'Shankhpushpi' for memory potentiating, tranquillizing properties and anxiolytic properties. Extracts of Evolvulus alsinoides as ethyl acetate, aqueous and Ethanolic have been seen antibacterial and anthelmintic properties and also to increase learning process and memory retention in rats [2,6] . ...
... In Indian system of Medicine (ISM), Amrita is an important drug which is used in medicine as rejuvenator or adaptogen, antioxidant, immunomodulatory, anti-inflammatory, anti-hyperglycaemic, antispasmodic, antiulcer and antistress properties for treating depression, Alzheimer disease, improving cerebral ischaemia, and attention-deficit hyperactivity disorder, oxidative stress injury and regulation of cytokines, memory enhancement by inhibiting reuptake of amines in brain and increased levels norepinephrine (NE), serotonin (5-hydroxytryptamine or 5-HT), dopamine (DA), and decreased levels of gammaaminobutyric acid (GABA) have been demonstrated. In herbal preparations, Tinospora cordifolia works synergistically for making the important component of polyherbal formulations for treating depression and various diseases [2,6,8] . ...
... It helps in memory enhancement by Arabian folklore. And also increases norepinephrine, epinephrine, dopamine and serotonin contents in the cerebral cortex and hippocampus [2,6,9] . ...
The main important aspect to differentiate from one individual to other human beings is Memory as it is important to recognize individual self. There are three basic forms of memory which allow the brain to encode, store, and retrieve. Without these basic forms of memory, individual even fails to build personal rapport, to acquire new knowledge, and unable to do basic functions of daily life. From last decades, Indian and Chinese cultures took interest for natural remedies by developing various traditional medicines from herbs for the declining activity of cognition, reverse memory loss and to increase learning power. Neotropic herbs are famous for brain acting herbs and smart drugs called from its isolated constituents as it helps to enhance circulation of blood in the brain. This Review focuses on natural agents and Herbs which act as memory boosters.
... Cognitive enhancers are drugs, supplements, nutraceuticals and functional foods that are purported to improve mental functions such as cognition, memory, intelligence, motivation, attention Secretariat for Higher Education, Science, Technology and Innovation and concentration (Tabassum (MP) has been used as human and animal nutritional supplement since ancient Aayurvedic tradition. MP has a been proposed as a cognitive enhancer Pranav, 2013;Kala and Mohan, 2010;Prias and Painni, 2009 MP supplements are of great interest due to the high nutritional value and low cost. The variety raw crude protein 32.4 g%, fat 5.7 g%, crude fiber 7.8 g%, ash 3.6 g%, carbohydrates 50.6 g% 262 g%, Mg 52.8 g%, P 457 g%,Fe 14.9 g%, Zn 3.76 g%, Mn 0.30 g%. ...
... Mucunapruriens (MP) has been used as human and animal nutritional supplement since ancient Aayurvedic tradition. MP has also been proposed as a cognitive enhancer (Tabassum et al., 2012;Pranav, 2013;Kala and Mohan, 2010;Prias and Painni, 2009 ) as nutritional supplement and cognitive enhancer in children", Glutamic acid. Total essential amino acids 39.8 g%, in vitro protein digestibility of 84.6% (Prias and Painni, 2009;Siddhuraju et al., 1996). ...
ARTICLE INFO ABSTRACT Mucunapruriens (MP) has been used in the Indian system of traditional medicine (Ayurveda been proposed as a cognitive enhancer and nutritional supplement due to the high nutritional value and low cost. The object of this study was to access nutritional supplement (NS) and cognitive enhancement (CE) qualities of MP in a group of schoo area of the City of Guayaquil, Ecuador. The universe consisted of 51, school children 6 out of a total school population of 120 students. A pediatric assessment was performed at the school through glucose, total protein physico were sustained for 6 weeks. After 6 weeks, analyzes were repeat Koppitz Test was selected to measure the maturity level of visual Prior to intervention, children manifested impulsive aggressive behavior and lacked the capacity to plan. After the intervent population. MP supplementation proves as a potential candidate for both nutritional and cognitive supplementation.
... Nonetheless, the treatment and management of memory loss is highly challenging [2] due to the fact that although approved therapies improve the symptoms, they cannot modify the course of illness nor cure it [3]. While it is evident that the brain is the center of the nervous system that controls processes such as memory, thought, reason, judgment, consciousness and emotion, supporting its health is indispensable to safeguard effective regulation and coordination of body functions [4,5]. This notion leads to a direction of nourishing the body as a mean to promote health which is consistent with an orthomolecular perspective. ...
... Nonetheless, the treatment and management of memory loss is highly challenging [2] due to the fact that although approved therapies improve the symptoms, they cannot modify the course of illness nor cure it [3]. While it is evident that the brain is the center of the nervous system that controls processes such as memory, thought, reason, judgment, consciousness and emotion, supporting its health is indispensable to safeguard effective regulation and coordination of body functions [4,5]. This notion leads to a direction of nourishing the body as a mean to promote health which is consistent with an orthomolecular perspective. ...
A short communitation on the novel concept of Orthomolecular Neuropsychology. Conceptualized as the comprehensive assessment of neuropsychological status from a sound psychometric, anatomical, physiological and nutritional standpoint.
Studies were carried out to determine if decreased levels of central nervous system docosahexaenoic acid (DHA), a result of
consuming an n-3-deficient diet, had an effect on learning- and memory-related behaviors in adult male rats. Females were
reared on an n-3-deficient or n-3-adequate diet beginning at 21 d of life. Their male pups, the F2 generation, were weaned
to the diet of the dam and tested at 9–12 wk of age. An olfactory-based discrimination and Morris water maze task were used
to assess performance. Whole brain was collected after the behavioral experiments and central nervous system fatty acid content
was analyzed in olfactory bulb total lipid extracts. F2 generation male rats consuming the n-3-deficient diet had an 82% decrease
in DHA compared to rats consuming the n-3-adequate diet. The n-3-deficient animals made significantly more total errors in
a 7-problem, 2-odor discrimination task compared to the n-3-adequate group. Furthermore, the escape latency in the Morris
water maze task was significantly longer for the n-3-deficient rats compared to the n-3-adequate rats. These results indicate
that rats with decreased DHA levels in the central nervous system perform poorer in these tasks compared to rats with higher
DHA levels and suggest the presence of learning deficits in these animals.
This study was designed to investigate the effect of sesaminol glycosides (SG), one of the most abundant lignan glycosides in sesame (Sesamum indicum LINN.) seed, on cognitive deficits and oxidative stress induced by intracerebroventricular (i.c.v.) injection of beta-amyloid protein (Abeta)(25-35) in mice. Mice were fed diets containing 0%, 0.25%, or 0.5% of SG for six weeks. Dietary SG showed a protective effect against Abeta-induced learning and memory deficits in passive avoidance and the Morris water maze test. Abeta caused significant neuronal loss in the CA1 and CA3 regions of the hippocampus, but SG supplement showed decrease of the Abeta(25-35) induced neuronal loss. The SG supplementation significantly decreased thiobarbituric acid reactive substance values and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in brain tissue. SG also reversed the activity of glutathione peroxidase (GPx), which is decreased by Abeta. These results suggest that SG protects against cognitive deficits induced by Abeta(25-35), in part through its antioxidant activity.
In the Ayurvedic system of medicine, the whole herb of 'Shankhpushpi' has been employed clinically for centuries for its memory potentiating, anxiolytic and tranquilizing properties. The present study was undertaken to investigate the effects of Evolvulus alsinoides (EA), considered as Shankhpushpi on learning and memory in rodents. Nootropic activity using Cook and Weidley's pole climbing apparatus, passive avoidance paradigms and active avoidance tests were used to test learning and memory. The ethanol extract of EA and its ethyl acetate and aqueous fractions were evaluated for their memory enhancing properties. Two doses (100 and 200 mg/kg p.o.) of the ethanol extract and ethyl acetate and aqueous fractions were administered in separate groups of animals. Both doses of all the extracts of EA significantly improved learning and memory in rats. Furthermore, these doses significantly reversed the amnesia induced by scopolamine (0.3 mg/kg i.p.). Nootropic activity was compared using piracetam as the standard. EA also exhibited potent memory enhancing effects in the step-down and shuttle-box avoidance paradigms.
Magnolol, honokiol, and obovatol are well-known bioactive constituents of the bark of Magnolia officinalis and have been used as traditional Chinese medicines for the treatment of neurosis, anxiety, and stroke. We recently isolated novel active compound (named 4-O-methylhonokiol) from the ethanol extract of Magnolia officinalis. The present study aimed to test two different doses of ethanol extracts of Magnolia officinalis (5 and 10 mg/kg/mouse, p.o., 1 week) and 4-O-methylhonokiol (0.75 and 1.5 mg/kg/mouse, p.o., 1 week) administered for 7 days on memory impairment induced by scopolamine (1 mg/kg body weight i.p.) in mice. Memory and learning were evaluated using the Morris water maze and the step-down avoidance test. Both the ethanol extract of Magnolia officinalis and 4-O-methylhonokiol prevented memory impairment induced by scopolamine in a dose-dependent manner. The ethanol extract of Magnolia officinalis and 4-O-methylhonokiol also dose-dependently attenuated the scopolamine-induced increase of acetylcholinesterase (AChE) activity in the cortex and hippocampus of mice, and inhibited AChE activity in vitro with IC(50) (12 nM). This study, therefore, suggests that the ethanol extract of Magnolia officinalis and its major ingredient, 4-O-methylhonokiol, may be useful for the prevention of the development or progression of AD.
Society must respond to the growing demand for cognitive enhancement. That response must start by rejecting the idea that 'enhancement' is a dirty word, argue Henry Greely and colleagues.
Immediate post-training intracerebroventricular administration to male mice of pregnenolone (P), pregnenolone sulfate (PS), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, or aldosterone caused improvement of retention for footshock active avoidance training, while estrone, estradiol, progesterone, or 16 beta-bromoepiandrosterone did not. Dose-response curves were obtained for P, PS, DHEA, and testosterone. P and PS were the most potent, PS showing significant effects at 3.5 fmol per mouse. The active steroids did not show discernible structural features or known membrane or biochemical effects that correlated with their memory-enhancing capacity. The above, together with the findings that DHEA acted even when given at 1 hr after training and that P, PS, and DHEA improved retention over a much wider dose range than do excitatory memory enhancers, led to the suggestion that the effects of the active steroids converge at the facilitation of transcription of immediate-early genes. P and PS, for which receptors have not yet been demonstrated, may exert their effects by serving as precursors for the formation of a panoply of different steroids, ensuring near-optimal modulation of transcription of immediate-early genes required for achieving the plastic changes of memory processes. Low serum levels of P in aging and the increases of cancer and behavioral disorders in individuals receiving drugs that block synthesis of cholesterol, the immediate precursor of P, suggest possible clinical utility for P.
Evidence of the importance of the B vitamins folic acid, vitamin B-12, and vitamin B-6 for the well-being and normal function of the brain derives from data showing neurologic and psychologic dysfunction in vitamin deficiency states and in cases of congenital defects of one-carbon metabolism. The status of these vitamins is frequently inadequate in the elderly and recent studies have shown associations between loss of cognitive function or Alzheimer disease and inadequate B vitamin status. The question that arises is whether these B vitamin inadequacies contribute to such brain malfunctions or result from aging and disease. From a theoretical standpoint, these inadequacies could give rise to impairment of methylation reactions that are crucial to the health of brain tissue. In addition or perhaps instead, these inadequacies could result in hyperhomocysteinemia, a recently identified risk factor for occlusive vascular disease, stroke, and thrombosis, any of which may result in brain ischemia. Advances in the understanding of this putative relation between inadequate vitamin status and loss of cognitive function in the elderly are likely to be slow and may depend on the outcomes of both prospective studies and longitudinal studies in which nutritional intervention is provided before cognitive decline occurs.
Classical eyeblink conditioning is a well-characterized model paradigm that engages the septohippocampal cholinergic system. This form of associative learning is impaired in normal aging and severely disrupted in Alzheimer's disease (AD). Some nicotinic cholinergic receptor subtypes are lost in AD, making the use of nicotinic allosterically potentiating ligands a promising therapeutic strategy. The allosterically potentiating ligand galantamine (Gal) modulates nicotinic cholinergic receptors to increase acetylcholine release as well as acting as an acetylcholinesterase (AChE) inhibitor. Gal was tested in two preclinical experiments. In Experiment 1 with 16 young and 16 older rabbits, Gal (3.0 mg/kg) was administered for 15 days during conditioning, and the drug significantly improved learning, reduced AChE levels, and increased nicotinic receptor binding. In Experiment 2, 53 retired breeder rabbits were tested over a 15-wk period in four conditions. Groups of rabbits received 0.0 (vehicle), 1.0, or 3.0 mg/kg Gal for the entire 15-wk period or 3.0 mg/kg Gal for 15 days and vehicle for the remainder of the experiment. Fifteen daily conditioning sessions and subsequent retention and relearning assessments were spaced at 1-month intervals. The dose of 3.0 mg/kg Gal ameliorated learning deficits significantly during acquisition and retention in the group receiving 3.0 mg/kg Gal continuously. Nicotinic receptor binding was significantly increased in rabbits treated for 15 days with 3.0 mg/kg Gal, and all Gal-treated rabbits had lower levels of brain AChE. The efficacy of Gal in a learning paradigm severely impaired in AD is consistent with outcomes in clinical studies.
A great deal of research has been devoted to the issue of whether the ingestion of a glucose containing drink facilitates cognitive performance. However, it remains unclear exactly how age and individual differences in gluco-regulatory control mediate a boost in cognitive functioning. The present study investigates these issues further. A repeated measures (25 g vs 50 g glucose vs placebo) counterbalanced, double-blind design was used with 25 younger and middle-aged adults. A battery of memory and non-memory tasks was administered; including tests of episodic and semantic memory, attention and visuospatial functioning. Glucose ingestion largely facilitated performance on tasks with a memory component. Notably, task demands and age (young vs middle-aged) contributed to the magnitude of memory enhancement. This finding suggests an age- and load-specific benefit of glucose intake. In addition, evidence suggests greater facilitation in individuals with good glucose regulation. These data are discussed in relation to the idea that glucose specifically affects neural mechanisms supporting memory functioning (i.e. the hippocampus), which are known to decline in ageing. Importantly, the present investigation adds to the growing body of literature showing the utility of glucose supplementation as memory enhancers.
Royal jelly (RJ) is known to have a variety of biological activities toward various types of cells and tissues of animal models, but nothing is known about its effect on brain functions. Hence, we examined the effect of oral administration of RJ on the mRNA expression of various neurotrophic factors, their receptors, and neural cell markers in the mouse brain. Our results revealed that RJ selectively facilitates the mRNA expression of glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and neurofilament H, a specific marker predominantly found in neuronal axons, in the adult mouse hippocampus. These observations suggest that RJ shows neurotrophic effects on the mature brain via stimulation of GDNF production, and that enhanced expression of neurofilament H mRNA is involved in events subsequently caused by GDNF. RJ may play neurotrophic and/or neuroprotective roles in the adult brain through GDNF.
Background
Methylphenidate (MPH) is the classic treatment for Attention Deficit Hyperactivity Disorder (ADHD), yet the mechanisms underlying its therapeutic actions remain unclear. Recent studies have identified an oral, MPH dose regimen which when given to rats produces drug plasma levels similar to those measured in humans. The current study examined the effects of these low, orally-administered doses of MPH in rats performing a delayed alternation task dependent on prefrontal cortex (PFC), a brain region that is dysfunctional in ADHD, and is highly sensitive to levels of catecholamines. The receptor mechanisms underlying the enhancing effects of MPH were explored by challenging the MPH response with the noradrenergic α2 adrenoceptor antagonist, idazoxan, and the dopamine D1 antagonist, SCH23390.
Results
MPH produced an inverted U dose response whereby moderate doses (1.0–2.0 mg/kg, p.o.) significantly improved delayed alternation performance, while higher doses (2.0–3.0 mg/kg, p.o.) produced perseverative errors in many animals. The enhancing effects of MPH were blocked by co-administration of either the α2 adrenoceptor antagonist, idazoxan, or the dopamine D1 antagonist, SCH23390, in doses that had no effect on their own.
Conclusion
The administration of low, oral doses of MPH to rats has effects on PFC cognitive function similar to those seen in humans and patients with ADHD. The rat can thus be used as a model for examination of neural mechanisms underlying the therapeutic effects of MPH on executive functions in humans. The efficacy of idazoxan and SCH23390 in reversing the beneficial effects of MPH indicate that both noradrenergic α2 adrenoceptor and dopamine D1 receptor stimulation contribute to cognitive-enhancing effects of MPH.
The correlation among the consumption of cocoa, chocolate and human health is not new. Throughout history it has been known that indigenous ancestors conferred special properties to these products which they called “Food of the Gods.” Experimental studies have pointed out the beneficial effects of consumption of cocoa and dark chocolate, thanks to their organic components. In addition to minerals and vitamins, they contain phytochemicals, polyphenols, tannins, theobromine, caffeine, theophylline and several neuroactive substances that act upon the nervous system. These substances affect emotions in a positive way and increase the sensation of energy, giving the feeling of pleasure obtained by the release of endorphins. On the other hand, specifically, the effect of polyphenols, and its high antioxidant capacity of dark chocolate have been associated with the delayed oxidation of low density lipoprotein, modification of lipid profile, reduction of insulin resistance and favors vasodilation dependent on nitric oxide. All these factors reduce cardiovascular risk and other pathologies. It is clearly demonstrated that cocoa components have an important antioxidant, anti-inflammatory and photo-protective role in pathologies (cognitive impairment, inflammatory bowel disease, dental health, skin photo-protection and cancer) in which inflammation is one of the main features, more clinical evidence is necessary to better understand and confirm the relevance of cocoa and chocolate polyphenols in human health. In this chapter, we will discuss about the evidences regarding the potential benefits of cocoa and dark chocolate in health.
Acorus calamus. Linn. (Araceae), commonly known as “sweet flag” or “calamus”, is a semiaquatic, perennial, aromatic herb with creeping rhizomes. The plant is found in the northern temperate and subtropical regions of Asia, North America, and Europe. The plant exhibits polyploidy. Many ethnomedicinal and ethnobotanical uses have been ascribed to the rhizomes of the plant. A. calamus. Linn. (AC) has been used as traditional Chinese and Indian prescriptions for its beneficial effects on memory disorder, learning performance, lipid peroxide content, and anti-aging and anticholinergic activity. Moreover, pharmacological studies have revealed that Acorus. rhizome and its constituents, particularly α.- and β.-asarone, possess a wide range of pharmacological activities such as sedative, CNS depressant, behavior modifying, anticonvulsant, acetylcholinesterase inhibitory, memory enhancing, anti-inflammatory, antioxidant, antispasmodic, cardiovascular, hypolipidemic, immunosuppressive, cytoprotective, antidiarrheal, antimicrobial, anthelmintic, insecticidal, adulticidal, diuretic, antioxidant, genotoxic, and mutagenic activities. This review is an effort to explore the different phytoconstituents and pharmacological activities of Acorus calamus..
Objective: To study the effect of Tinospora cordifolia (Tc) on learning and memory in normal and cyclosporine induced memory deficit rats. Methods: Alcoholic and aqueous extracts of the whole plant of Tinospora cordifolia was administered orally for 15 days in two groups of rats. Cyclosporine 15, 25 mg/kg, i.p. was administered on alternate days for 10 days. Combination of cyclosporine 25 mg/kg, i.p. for 10 days and Tc alcoholic 200 mg/kg and Tc aqueous 100 mg/kg were administered in two different groups of rats. At the end of treatment, learning and memory was assessed using Hebb William maze and passive avoidance task. The locomotor activity was assessed using open field chamber. The immune status was studied using DNCB skin sensitivity test. Histopathological examination of hippocampus was done. Results: Both alcoholic and aqueous extracts of Tc produced a decrease in learning scores in Hebb William maze and retention memory indicating enhancement of learning and memory. However, cyclosporine at both the doses increased the learning scores in Hebb William maze and decrease in retention time in the passive avoidance task suggesting a memory deficit. The combination of cyclosporine and Tc produced a decrease in learning scores in Hebb William maze and increase latency in passive avoidance task compared to cyclosporine alone treated rats. The histopathological examination of hippocampus in cyclosporine treated rats showed neurodegenerative changes which were protected by the Tc. Conclusion: Tc enhances cognition (learning and memory) in normal rats. Cyclosporine induced memory deficit was successfully overcome by Tc.
Eleutherococcus senticosus Maxim., classified into the family of Araliaceae, is used in a variety of diseases in traditional Korean medicine including ischemic heart disease.
To determine the neuroprotective effects of Eleutherococcus senticosus on global cerebral ischemia.
A four-vessel occlusion (4-VO) rat model was used to evaluate the potential protective effects against transient global cerebral ischemia ethanol extracts of Eleutherococcus senticosus was orally administered at doses of 3, 30, and 300 mg/kg twice at times of 0 and 90 min after reperfusion. The effects on memory deficit were investigated by using a Y-maze neurobehavioral test after brain ischemia, and the effects on hippocampal neuronal damage were measured 7 days after ischemia. The expressions of glial fibrillary acid protein (GFAP), CD11b antibody (OX-42), and cyclooxygenase-2 (COX-2) were investigated by immunohistochemistry.
Oral administration of Eleutherococcus seticosus at 30, 100 and 300 mg/kg significantly reduced hippocampal CA1 neuronal death by 3.5%, 25.9% and 53.1%, respectively, compared with a vehicle-treated group. Oral administration of Eleutherococcus senticosus at 300 mg/kg inhibited 81.9% of the decrease in spontaneous alternation induced by 4-VOin the Y-maze test, and also attenuated ischemia-induced activation of COX-2, GFAP and OX-42 in the hippocampal CA1 region.
Eleutherococcus senticosus protects delayed neuronal death in the CA1 region of the hippocampus against global cerebral ischemia in rats with the recovery of spatial memory, which can be considered as the normal functioning of the hippocampus. Regarding the immunohistochemical study, the effect of Eleutherococcus senticosus may be attributable to its anti-inflammatory properties through the inhibition of COX-2 expression, microglia and astrocyte expression.
This study investigated the effect of Rhodiola rosea L. extract on acquisition and expression of morphine tolerance and dependence in mice. Therefore animals were injected with repeated administration of morphine (10 mg/kg, subcutaneous) twice daily for five or six days, in order to make them tolerant or dependent. Rhodiola rosea L. extract (0, 10, 15 and 20 mg/kg) was administered by the intragastric route 60 min prior to each morphine injection (for acquisition) or prior the last injection of morphine or naloxone on test day (for tolerance or dependence expression, respectively). Morphine tolerance was evaluated by testing its analgesic effect in the tail flick test at the 1st and 5th days. Morphine dependence was evaluated by counting the number of withdrawal signs (jumping, rearing, forepaw tremor, teeth chatter) after naloxone injection (5 mg/kg; intraperitoneal) on the test day (day 6). Results showed that Rhodiola rosea L. extract significantly reduced the expression of morphine tolerance, while it was ineffective in modulating its acquisition. Conversely, Rhodiola rosea L. extract significantly and dose-dependently attenuated both development and expression of morphine dependence after chronic or acute administration. These data suggest that Rhodiola rosea L. may have human therapeutic potential for treatment of opioid addiction.
Peganum harmala L. is a multipurpose medicinal plant increasingly used for psychoactive recreational purposes (Ayahuasca analog). Harmaline, harmine, harmalol, harmol and tetrahydroharmine were identified and quantified as the main beta-carboline alkaloids in P. harmala extracts. Seeds and roots contained the highest levels of alkaloids with low levels in stems and leaves, and absence in flowers. Harmine and harmaline accumulated in dry seeds at 4.3% and 5.6% (w/w), respectively, harmalol at 0.6%, and tetrahydroharmine at 0.1% (w/w). Roots contained harmine and harmol with 2.0% and 1.4% (w/w), respectively. Seed extracts were potent reversible and competitive inhibitors of human monoamine oxidase (MAO-A) with an IC(50) of 27 microg/l whereas root extracts strongly inhibited MAO-A with an IC(50) of 159 microg/l. In contrast, they were poor inhibitors of MAO-B. Inhibition of MAO-A by seed extracts was quantitatively attributed to harmaline and harmine whereas inhibition by root extracts came from harmine with no additional interferences. Stems and leaves extracts were poor inhibitors of MAO. The potent inhibition of MAO-A by seed and root extracts of P. harmala containing beta-carbolines should contribute to the psychopharmacological and toxicological effects of this plant and could be the basis for its purported antidepressant actions.
Several studies have revealed piperine and a few related compounds as potent inhibitors of monoamine oxidases without delineating the underlying mechanism. Using in silico modelling, we propose a structural basis of such activity by showing that these compounds can successfully dock into the inhibitor binding pockets of human monoamine oxidase isoforms with predicted affinities comparable to some known inhibitors. The results therefore suggest that piperine can be a promising lead for developing novel monoamine oxidase inhibitors.
The polyphenolics in fruits and vegetables, when fed to rats from 19-21 months of age, have been shown to retard and even reverse age-related decrements in motor and cognitive performance. These effects may be the result of the polyphenols increasing antioxidant and/or anti-inflammatory levels, or by direct effects on signaling, in the brain. Increased dietary intake of berry fruit, in particular, has a positive and profound impact on human health, performance, and disease. Thus, the present study examined a 2% blackberry-supplemented diet for its effectiveness in reversing age-related deficits in behavioral and neuronal function when fed to aged (19-month-old) Fischer 344 rats for 8 weeks. The results showed that the blackberry diet improved motor performance on three tasks which rely on balance and co-ordination: the accelerating rotarod, wire suspension, and the small plank walk. Results for the Morris water maze showed that the blackberry-fed rats had significantly greater working, or short-term, memory performance than the control rats. These data support our previous investigations in which we have seen improved motor and cognitive performance in aged rats after supplementation with other berry fruits.
Rhodiola rosea L. (Crassulaceae) is traditionally used in Eastern Europe and Asia to stimulate the nervous system, enhance physical and mental performance, treat fatigue, psychological stress and depression. In order to investigate the influence of Rhodiola rosea L. roots on mood disorders, three extracts were tested against monoamine oxidases (MAOs A and B) in a microtitre plate bioassay.
Methanol and water extracts gave the highest inhibitory activity against MAOs. Twelve compounds were then isolated by bioassay-guided fractionation using chromatographic methods. The structures were determined by 1H, 13C NMR and HR-MS.
The methanol and water extracts exhibited respectively inhibitions of 92.5% and 84.3% on MAO A and 81.8% and 88.9% on MAO B, at a concentration of 100 microg/ml. The most active compound (rosiridin) presented an inhibition over 80% on MAO B at a concentration of 10(-5) M (pIC50=5.38+/-0.05).
The present investigation demonstrates that Rhodiola rosea L. roots have potent anti-depressant activity by inhibiting MAO A and may also find application in the control of senile dementia by their inhibition of MAO B.
Aim of the study:
Ilex paraguariensis St. Hilaire (Aquifoliaceae) is a plant widely cultivated in South America that is used to prepare a tea-like beverage with a reputation to improve cognitive function, a response that has been attributed to the constituents of the leaves, especially caffeine. Our previous study indicated that the hydroalcoholic extract of Ilex paraguariensis presents an antiparkinsonian profile in reserpine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated rodents.
Materials and methods:
In the present study, the effects of the hydroalcoholic extract of Ilex paraguariensis on the short- and long-term learning and memory of rats were assessed with the social recognition, Morris water maze, and step-down inhibitory avoidance tasks.
Results:
A preliminary HPLC fingerprint of the plant extract confirmed the presence of caffeine (the major compound), rutin and kaemperol, and revealed the absence of detectable concentrations of caffeic acid, quercetin and ursolic acid. Acute pre-training intraperitoneal (i.p.) or oral administration of the extract of Ilex paraguariensis improved the short-term social memory in a specific manner as well as facilitated the step-down inhibitory avoidance short-term memory evaluated 1.5h after training. Moreover, a synergistic response was observed following the co-administration of 'non-effective' doses of caffeine and Ilex paraguariensis in the social memory. In contrast, pre-training administration of hydroalcoholic extract of Ilex paraguariensis did not alter the step-down inhibitory avoidance long-term memory evaluated 24h after training, while the highest dose tested (250 mg/kg, i.p.) disrupted the animals' performance in a cued version of the Morris water maze.
Conclusion:
These results partly substantiate the traditional use of mate tea for improvement of cognition indicating that acute administration of hydroalcoholic extract of Ilex paraguariensis differentially modulates short- and long-term learning and memory in rats probably through its antagonist's action on adenosine receptors.
There is currently considerable interest in the potential health benefits of isoflavones in functional foods and in the future prospects for the development of new products of benefit to the consumer. The potential health benefits of isoflavones may include protection against age-related diseases including cardiovascular disease, osteoporosis, hormone-dependent cancer and loss of cognitive function. The mechanisms involved may include weak oestrogenic action and antioxidant activity. Our proteomic investigations of changes in the human serum profile in response to the consumption of isoflavones in soya functional foods suggest potentially beneficial modulation of the levels of a number of serum proteins, including increased apolipoprotein E (involved in lipid metabolism) and caeruloplasmin (antioxidant and copper regulatory properties) levels and decreased alpha-1-acid glycoprotein (involved in immunomodulation) levels that may contribute to vascular protection. Furthermore, preliminary metabonomic data indicates an alteration in the urinary metabolite profile after isoflavone consumption, which may be of significance.
1. Spiroperidol binding (dopamine D2 receptors) and quinuclidinyl benzilate binding (muscarinic receptors) in striata of 19-month old mice was analyzed for animals that had received chronic administration of cytidine 5'-diphosphocholine (CDP-choline) incorporated into the chow consumed (100 or 500 mg kg-1 added per day) for the 7 months before they were killed. 2. Treated animals displayed an increase in the dopamine receptor densities of 11% for those receiving 100 mg kg-1 and 18% for those receiving 500 mg kg-1 as compared to the control aged animals that had received no CDP-choline. Control animals showed, from 2 months to 19 months of life, a 28% decrease in the receptor density. No change in the affinity of the receptors for spiroperidol was found in the treated or untreated animals. 3. Muscarinic acetylcholine receptor densities were also partially recovered by the same treatment in aged animals that showed a 14% decrease of these receptors in this case. The muscarinic receptor density increased 6% for the animals that received 100 mg kg-1 and 17% for the animals that received 500 mg kg-1 without any change in the affinity of the receptor for quinuclidinyl benzilate. 4. Aged animals displayed a slight increase in brain membrane fluidity as indicated by a decrease in the polarization value of the non-polar fluorophore 1,6-diphenyl-1,3,5-hexatriene. Interestingly, in the treated animals a greater increase in membrane fluidity was determined and found to be very similar for the two doses.5. It is concluded that chronic administration of CDP-choline to aged animals promoted a partial recovery of the striatum dopamine and acetylcholine receptor function normally reduced with aging, which might be explicable in terms of mechanisms involving fluidity of the brain neuronal membrane.
We studied the metabolic effects of high dietary intakes of pyridoxine and of the substrate-cofactor interaction between dietary histidine or tryptophan and pyridoxine in rat brain. In the substrate-cofactor interaction study, histamine and serotonin levels were determined in rats fed elevated or requirement levels of substrate (histidine: 0.3% and 0.8%, tryptophan: 0.15% and 0.6%) and excess or requirement levels of pyridoxine HCl (7 mg vs. 3,000 mg/kg). Excess pyridoxine intake caused a differential effect on brain histamine concentration--inhibitory with the requirement level of histidine (-29%), and stimulatory (+21%) with the elevated level of histidine. When dietary tryptophan was fed at the requirement level, excess pyridoxine caused essentially no changes in hypothalamic serotonin and 5HIAA (-2%, -2%). With elevated tryptophan intake, excess pyridoxine significantly increased serotonin and 5HIAA (+32%, +20%) in the hypothalamus. These results indicate a clear interaction between substrate and coenzyme precursor which influences brain metabolism of histamine and serotonin.
The exposure of cultured rat striatal neurons to L-DOPA caused marked cell death. The L-DOPA cytotoxicity was inhibited by the addition of Mg2+ to and by the removal of Ca2+ from the culture medium, and also by the application of tetrodotoxin. Moreover, prolonged application of L-DOPA increased the glutamate content in the culture medium. These results indicate that L-DOPA produces neurotoxicity by facilitating glutamate release.
Hypericum perforatum L. (St. John's Wort) is a complex herb that has been used for centuries for its putative medicinal properties, and has current therapeutic relevance as a treatment of mild to moderate depression. Recently, two studies in rodents have suggested that hypericum may also have memory-enhancing effects. It has a complex pharmacology, in that acute administration modulates numerous neurotransmitter systems that have previously been observed to either augment or impair a variety of memory processes in humans. This study aimed to examine whether acute administration of standardized hypericum extract could exert a nootropic effect in normal human subjects. The study employed a double-blind, crossover, repeated-measures design. Twelve healthy young subjects completed the Cognitive Drug Research (CDR) memory battery, following administration of placebo, 900 mg and 1800 mg hypericum (Blackmore's Hyperiforte). The findings suggested that hypericum does not have an acute nootropic effect in healthy humans at these doses. However, there was some evidence for an impairing effect on accuracy of numeric working memory and delayed picture recognition at the higher dose. This observed impairment could be due to a sensitivity of these specific tasks to modulation by neurotransmitters that have been noted to have memory-impairing effects (e.g. y-aminobutyric acid (GABA), serotonin).
Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with head traumas, stroke, age and age-related pathologies. Development of cognition enhancers is still a difficult task because of complexity of the brain functions, poor predictivity of animal tests and lengthy and expensive clinical trials. After the early serendipitous discovery of first generation cognition enhancers, current research is based on a variety of working hypotheses, derived from the progress of knowledge in the neurobiopathology of cognitive processes. Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety. In the present review, after a general discussion of the problems connected with the design and development of cognition enhancers, the class is examined in more detail. Reasons for the problems encountered by nootropics, compounds therapeutically available and those in development, their structure activity relationships and mechanisms of action are discussed. Recent developments which hopefully will lead to a revival of the class are reviewed.
To review the role of essential fatty acids in brain membrane function and in the genesis of psychiatric disease.
Medline databases were searched for published articles with links among the following key words: essential fatty acids, omega-3 fatty acids, docosahexanoic acid, eicosapentanoic acid, arachidonic acid, neurotransmission, phospholipase A2, depression, schizophrenia, mental performance, attention-deficit hyperactivity disorder, and Alzheimer's disease. Biochemistry textbooks were consulted on the role of fatty acids in membrane function, neurotransmission, and eicosanoid formation. The 3-dimensional structures of fatty acids were obtained from the Web site of the Biochemistry Department, University of Arizona (2001).
The fatty acid composition of neuronal cell membrane phospholipids reflects their intake in the diet. The degree of a fatty acid's desaturation determines its 3-dimensional structure and, thus, membrane fluidity and function. The ratio between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), in particular, influences various aspects of serotoninergic and catecholaminergic neurotransmission, as shown by studies in animal models. Phospholipase A2 (PLA2) hydrolyzes fatty acids from membrane phospholipids: liberated omega-6 PUFAs are metabolized to prostaglandins with a higher inflammatory potential, compared with those generated from the omega-3 family. Thus the activity of PLA2 coupled with membrane fatty acid composition may play a central role in the development of neuronal dysfunction. Intervention trials in human subjects show that omega-3 fatty acids have possible positive effects in the treatment of various psychiatric disorders, but more data are needed to make conclusive directives in this regard.
The ratio of membrane omega-3 to omega-6 PUFAs can be modulated by dietary intake. This ratio influences neurotransmission and prostaglandin formation, processes that are vital in the maintenance of normal brain function.
Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults.
Tetrahydropapaveroline (THP) is formed in Parkinsonian patients receiving L-DOPA therapy and is detected in the plasma and urine of these patients. In this study, we have investigated the effects of THP on L-DOPA-induced neurotoxicity in cultured rat adrenal pheochromocytoma, PC12 cells. Exposure of PC12 cells up to 10 microM THP or 20 microM L-DOPA after 24 or 48 hr, neither affected the cell viability determined by MTT assay, nor induced apoptosis by flow cytometry and TUNEL staining. However, at concentrations higher than 15 microM, THP showed cytotoxicity through an apoptotic process. In addition, THP at 5-15 microM for both incubation time points significantly enhanced L-DOPA-induced neurotoxicity (L-DOPA concentration, 50 microM). Exposure of PC12 cells to THP, L-DOPA and THP plus L-DOPA for 48 hr resulted in a marked increase in the cell loss and percentage of apoptotic cells compared with exposure for 24hr. The enhancing effects of THP on L-DOPA-induced neurotoxicity were concentration- and treated-time-dependent. THP, L-DOPA and THP plus L-DOPA produced a significant increase in intracellular reactive oxygen species generation and decrease in ATP levels, supporting the involvement of oxidative stress in THP- and L-DOPA-induced apoptosis. The antioxidant N-acetyl-L-cysteine strongly inhibited changes in apoptosis, decreases in cell viability and ROS generation induced by THP associated with L-DOPA. These results suggest that THP aggravates L-DOPA-induced oxidative neurotoxic and apoptotic effects in PC12 cells. Therefore, Parkinsonian patients treated with L-DOPA for long-term need to be monitored for the relationship between plasma concentration of THP and the symptoms of neurotoxicity.
In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza glabra (family: Leguminosae) have been employed clinically for centuries for their anti-inflammatory, antiulcer, expectorant, antimicrobial and anxiolytic activities. The present study was undertaken to investigate the effects of Glycyrrhiza glabra (popularly known as liquorice) on learning and memory in mice. Elevated plus-maze and passive avoidance paradigm were employed to test learning and memory. Three doses (75, 150 and 300 mg/kg p.o.) of aqueous extract of Glycyrrhiza glabra were administered for 7 successive days in separate groups of animals. The dose of 150 mg/kg of the aqueous extract of liquorice significantly improved learning and memory of mice. Furthermore, this dose significantly reversed the amnesia induced by diazepam (1 mg/kg i.p.) and scopolamine (0.4 mg/kg i.p.). Anti-inflammatory and antioxidant properties of liquorice may be contributing favorably to the memory enhancement effect. Since scopolamine-induced amnesia was reversed by liquorice, it is possible that the beneficial effect on learning and memory was due to facilitation of cholinergic-transmission in mouse brain. However, further studies are necessitated to identify the exact mechanism of action. In the present investigation, Glycyrrhiza glabra has shown promise as a memory enhancing agent in all the laboratory models employed.
Three studies using healthy volunteers (n = 271) investigated the effects of caffeine, carbohydrates and carbonation in functional "energy" drinks (EDs) with the aim of determining their benefit in every-day life. The results showed caffeine to be the main ED constituent responsible for the effects found, with possible minor, relatively weak effects of carbohydrates. EDs were found to improve and/or maintain mood and performance during fatiguing and cognitively demanding tasks relative to placebo. In terms of absolute values, EDs maintained levels of arousal compared to a deterioration in arousal where placebo was consumed. These effects were found in caffeine-deprived participants, and so may be largely due to "withdrawal reversal". There were only minor differences in the effects of water vs. "sensory-matched" placebo, supporting previous findings indicating that the type of placebo does not alter the conclusions drawn about the effects of the full ED. Finally, carbonation had various effects on mood, some of which were present immediately following consumption, others were consistent with slower absorption of caffeine (and possibly carbohydrates) from carbonated drinks.
Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicinal formula, which has been used effectively to treat depression-related diseases in China. There is no information available about the antidepressant activity of curcumin, the active component of curcuma longa. In the present study, we analyzed the effects of curcumin on depressive-like behaviors in mice, using two animal models of depression. Our results showed that curcumin treatment at 5 and 10 mg/kg (p.o.) significantly reduced the duration of immobility in both the tail suspension and forced swimming tests. These doses that affected the immobile response did not affect locomotor activity. In addition, the neurochemical assays showed that curcumin produced a marked increase of serotonin and noradrenaline levels at 10 mg/kg in both the frontal cortex and hippocampus. Dopamine levels were also increased in the frontal cortex and the striatum. Moreover, curcumin was found to inhibit monoamine oxidase activity in the mouse brain. These findings suggest that the antidepressant-like effects of curcumin may involve the central monoaminergic neurotransmitter systems.
Huperzia saururus (Lam.) Trevis. (Lycopodiaceae) known as cola de quirquincho is used in folk medicine to improve memory. The cholinergic neurons of the basal forebrain, including those in the medial septum, and in the vertical limbs of the diagonal band of Broca and the nucleus basalis of Meynert, provide a major source of cholinergic enervation of the cortex and hippocampus. These neurons have also been shown to play an important role in learning and memory processes. Thus, the effects of this traditional Argentinean species were studied in relation to its activity on synaptic transmission in the hippocampus. The alkaloid extract obtained first by decoction of the aerial parts and by subsequent alkaline extraction, was purified by using a Sephadex LH 20 packed column. Electrophysiological experiments were developed with the purified extract (E(2)) on rat hippocampus slices, thus eliciting long-term potentiation (LTP). Results show a marked increase in the hippocampal synaptic plasticity. The threshold value for generation of LTP was 22 +/- 1.01 Hz on average for E(2), while for controls it was 86 +/- 0.92 Hz. All of these factors could explain the use of Huperzia saururus as a memory improver as is reported in the ethnomedicine.
This study investigated for the first time the potential effects of cis- and trans-resveratrol (c-RESV and t-RESV) on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake by synaptosomes from rat brain, on 5-HT uptake by human platelets, and on monoamine oxidase (MAO) isoform activity. Both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the uptake of [3H]NA and [3H]5-HT by synaptosomes from rat brain and the uptake of [3H]5-HT by human platelets. In both experimental models, t-RESV was slightly more efficient than c-RESV. Furthermore, in synaptosomes from rat brain, the RESV isomers were less selective against [3H]5-HT uptake than the reference drug fluoxetine (0.1-30 microM). On the other hand, both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the enzymatic activity of commercial (human recombinant) MAO isoform (MAO-A and MAO-B) activity, c-RESV being slightly less effective than t-RESV. In addition, both RESV isomers were slight but significantly more selective against MAO-A than against MAO-B. Since the principal groups of drugs used in the treatment of depressive disorders are NA/5-HT uptake or MAO inhibitors, under the assumption that the RESV isomers exhibit a similar behaviour in humans in vivo, our results suggest that these natural polyphenols may be of value as structural templates for the design and development of new antidepressant drugs with two important biochemical activities combined in the same chemical structure: NA/5-HT uptake and MAO inhibitory activity.
Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients and reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Delta9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of Abeta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.
The learning and memory deficits have been recognized as severe and consistent neurological disorders associated with numerous neurodegenerative states. Research in this area has gained momentum only in the recent past after the biochemical and physiological basis of these processes have been understood. A considerable alteration in the neurotransmission is a consistent finding in cognitive disorders. Therefore, many therapeutic strategies to augment the concentration of neurotransmitters in brain such as cholinergic agents, biogenic amines and neuropeptides etc. have been evaluated in cognitive deficits. CNS modulators are the type of antiamnesics that act via modulation of the neurological processes underlying memory storage. These include psychostimulants, excitatory amino acids and most important of all "nootropics". Nootropics are a heterogeneous group of compounds of diverse chemical composition and biological function that allegedly facilitate learning and memory or overcome natural or induced cognitive impairments. The literature survey incorporated in this article hallmarks the success achieved in the design and development of potential nootropic agents. Additionally, this review is an attempt towards discussing various approaches available to enhance memory, along with the classification of the known memory enhancers, authors research work towards various structural modifications carried out and the biological screening.
Ayurveda means "the science of life". Ayur means "life" and Veda means "knowledge or science". It is the oldest medical system in the world. Its origins can be traced as far back as 4500 BC, to four ancient books of knowledge, (the "Vedas") and it is still officially recognized by the government of India. The present study was aimed at investigating the effects of Anwala churna (Emblica officinalis Gaertn.), an Ayurvedic preparation on memory, total serum cholesterol levels and brain cholinesterase activity in mice. Anwala churna was administered orally in three doses (50, 100 and 200 mg/kg) for fifteen days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. Total serum cholesterol levels and brain cholinesterase activity also estimated. Anwala churna (50, 100 and 200 mg/kg, p.o.) produced a dose-dependent improvement in memory scores of young and aged mice. Furthermore, it reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, brain cholinesterase activity and total cholesterol levels were reduced by Anwala churna administered orally for 15 days. Anwala churna may prove to be a useful remedy for the management of Alzheimer's disease on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.
Gugulipid, an ethyl acetate extract of the resin of plant Commiphora whighitii is an established hypolipidemic agent in clinical practice. The major constituent of gugulipid is guggulsterone [4, 17 (20)-pregnadiene-3, 16-dione]. It has been observed recently that patients receiving lipid-lowering drugs like statins have a reduced risk of dementia. Therefore, the present study was planned to explore the potential of gugulipid as cognitive enhancer. Gugulipid (12.5, 25 and 50 mg/kg, p.o.) showed dose dependent improvement in scopolamine-induced deficits in passive avoidance test. The maximal effective dose of gugulipid i.e. 50 mg/kg, p.o. was used for further studies on streptozotocin (STZ) model of dementia in mice. Gugulipid was investigated for its effect on learning and memory, parameters of oxidative stress (GSH and MDA) and acetylcholinesterase (AChE) activity in the STZ (ic)-treated mice. Intracerebral (ic) injections of STZ (0.5 mg/kg) on 1st and 3rd day caused significant deficit in memory in passive avoidance and Morris water maze test after the 14th day of first dose. In passive avoidance, transfer latency time (TLT) was not increased on retention trials in STZ (ic) group while gugulipid treatment resulted in significant increase in TLT on retention trials in STZ (ic)-treated mice. In Morris water maze test the latency time to reach platform in STZ (ic)-treated mice was significantly higher than control and vehicle (artificial CSF). Pre-treatment of gugulipid (50 mg/kg, p.o.) daily for 14 days started with the first dose of STZ (ic), significantly prevented STZ (ic)-induced memory deficit. Post-treatment i.e. after 14 days of first dose of STZ (ic) of gugulipid (50 mg/kg, p.o.) significantly decreased the latency time indicating anti-dementia activity. Effect of gugulipid and STZ in visible platform test was similar to those seen with hidden platform. Gugulipid and STZ-treated mice did not cause significant change in locomotor activity. Furthermore, STZ (ic) resulted into increase in AChE activity, low level of GSH and high concentration of MDA in brain on 21st day as compared to control. Gugulipid treatment caused significant decrease in AChE activity, low level of MDA and high concentration of GSH in brain following STZ (ic) as compared to vehicle administration in STZ (ic)-treated mice. The study demonstrated that gugulipid has significant protective affect against streptozotocin-induced memory deficits model of dementia that can be attributed to anti-oxidant and anti-AChE activity of gugulipid. These observations suggest gugulipid as a potential anti-dementia drug (CDRI, Lucknow has obtained US patent No. 6896901 for use of gugulipid as cognitive enhancer).
In this study, we tested preventive effects of a natural medicine the extract of Ginkgo biloba (EGB 761) on post-stress cognitive dysfunction. Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and have been linked to the pathophysiology of mood and anxiety disorders. Our findings indicate that chronic restraint stress impaired egocentric spatial memory as observed in the eight-arm radial maze but it did not alter the allocentric spatial memory in the Morris water maze. In control rats EGB 761 (100mg/kg, orally) improved spatial memory in these two tests. Also, EGB 761 normalized cognitive deficits seen in rats chronically stressed or treated with an 'equivalent' dose of exogenous corticosterone (5mg/kg, subcutaneously). We conclude that, in rats, repeated administration of EGB 761 prevents stress- and corticosterone-induced impairments of spatial memory.
Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4,000 and 4,500 m altitude in the central Peruvian Andes, particularly in Junin plateau. Previously, Black variety of Maca showed to be more beneficial than other varieties of Maca on learning and memory in ovariectomized mice on the water finding test. The present study aimed to test two different doses of aqueous (0.50 and 2.00 g/kg) and hydroalcoholic (0.25 and 1.00 g/kg) extracts of Black Maca administered for 35 days on memory impairment induced by scopolamine (1mg/kg body weight i.p.) in male mice. Memory and learning were evaluated using the water Morris maze and the step-down avoidance test. Brain acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities in brain were also determined. Both extracts of Black Maca significantly ameliorated the scopolamine-induced memory impairment as measured in both the water Morris maze and the step-down avoidance tests. Black Maca extracts inhibited AChE activity, whereas MAO activity was not affected. These results indicate that Black Maca improves scopolamine-induced memory deficits.
Neural stem/progenitor cells (NSCs) proliferate vigorously as neurospheres in medium containing basic fibroblast growth factor (FGF-2), but start differentiating into neurons, astrocytes or oligodendrocytes in FGF-2-free medium. An extract of royal jelly (RJ) significantly increased the percentage in the total cell population of not only neurons immunoreactive for class III beta-tubulin (Tuj1) but also astrocytes immunoreactive for glial fibrillary acidic protein (GFAP), and oligodendrocytes immunoreactive for 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) generated from NSCs, but decreased that of nestin-positive NSCs. These results highlight a novel and outstanding property of the RJ, i.e., that it facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes). On the other hand, 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid characteristic of RJ, increased the generation of neurons and decreased that of astrocytes from NSCs. These observations suggest that RJ contains plural components that differently influence neuronal and/or glial lineages and that HDEA is one of such components of RJ that facilitates neurogenesis by NSCs.
Memory, attention and creativity represent three different cognitive domains, which are interconnected and contribute the “mental performance” of an individual. Modern neuroscience has investigated some of the neuronal circuits and of the neurotransmitters and molecular events underlying the above-mentioned cognitive functions. Within this renewed reference context, some of the properties of the components of the remedies to increase mental performance have been studied and validated in experimental models and, to date, these substances are named “smart drugs”, “memory enhancing drugs” or “nootropic drugs” (from the Greek root noos for mind and tropein for toward). Recently pharmaceutical industries are increasingly focusing on the research for potential substances in this field: several “smart drugs” are in clinical trials and could be on the market in few years. Furthermore, a quick survey from Internet highlights the presence of a great variety of both approved and non-approved drugs, with some of them addressing to only medical and others to performance-oriented use, opening room to some reflections or speculations from scientific and ethical points of view.
It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness.
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