A comprehensive review on tissue culture studies and secondary metabolite production in Bacopa monnieri L. Pennell: a nootropic plant.

Bacopa monnieri L. Pennell, commonly known as Brahmi, is an important medicinal plant that belongs to the family Plantaginaceae. Brahmi is rich in innumerable bioactive secondary metabolites, especially bacosides that can be employed to reduce many health issues. This plant is used as a neuro-tonic and treatment for mental health, depression, and cognitive performance. Brahmi is also known for its antioxidant, anti-inflammatory, and anti-hepatotoxic activities. There is a huge demand for its raw materials, particularly for the extraction of bioactive molecules. The conventional mode of propagation could not meet the required commercial demand. To overcome this, biotechnological approaches, such as plant tissue culture techniques have been established for the production of important secondary metabolites through various culture techniques, such as callus and cell suspension cultures and organ cultures, to allow for rapid propagation and conservation of medicinally important plants with increased production of bioactive compounds. It has been found that a bioreactor-based technology can also enhance the multiplication rate of cell and organ cultures for commercial propagation of medicinally important bioactive molecules. The present review focuses on the propagation and production of bacoside A by cell and organ cultures of Bacopa monnieri, a nootropic plant. The review also focuses on the biosynthesis of bacoside A, different elicitation strategies, and the over-expression of genes for the production of bacoside-A. It also identifies research gaps that need to be addressed in future studies for the sustainable production of bioactive molecules from B. monnieri.

Study on Mechanism of Ginkgo biloba L. Leaves for the Treatment of Neurodegenerative Diseases Based on Network Pharmacology.

Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs). In this study, network pharmacology was employed to elucidate potential mechanism of GBLs in the treatment of NDs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the chemical components in accordance with the screening principles of oral availability and drug-like property. Potential targets of GBLs were integrated with disease targets, and intersection targets were exactly the potential action targets of GBLs for treating NDs; these key targets were enriched and analyzed by the protein protein interaction (PPI) analysis and molecular docking verification. Key genes were ultimately used to find the biological pathway and explain the therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-seven active components of GBLs may affect biological processes such as oxidative reactions and activate transcription factor activities. These components may also affect 120 metabolic pathways, such as the PI3K/AKT pathway, by regulating 147 targets, including AKT1, ALB, HSP90AA1, PTGS2, MMP9, EGFR and APP. By using the software iGEMDOCK, the main target proteins were found to bind well to the main active components of GBLs. GBLs have the characteristics of multi-component and multi-target synergistic effect on the treatment of NDs, which preliminarily predicted its possible molecular mechanism of action, and provided the basis for the follow-up study.

Epigallocatechin Gallate Reduces Amyloid ß-Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.

SCOPE: We investigated the role of endoplasmic reticulum (ER) stress in the protective effects of EGCG against the neuronal apoptosis in Aß1-42 -induced SH-SY5Y cells and APP/PS1 transgenic mice. METHODS AND RESULTS: Cell viability (CCK8 assay), flow cytometry, Hoechst 33258 staining, immunohistochemistry, transmission electron microscopy (TEM), and western blotting were used. EGCG prevented Aß1-42-induced toxicity in SH-SY5Y cells, increased cell viability, and decreased apoptosis in a dose-dependent manner. In a subsequent mechanism study, it was found that this effect contributed to the down-regulation of GRP78, CHOP, cleaved-caspase-12 and -3. Moreover, EGCG also reduced the cytotoxicity induced by tunicamycin (TM) and thapsigargin (TG), two ER stress activators. Consistent with the in vitro study, EGCG inhibited neuronal apoptosis in the cortex of APP/PS1 transgenic mice, with the mitigation of ER abnormal ultrastructural swelling and the downregulation of ER-stress-associated proteins. CONCLUSION: These results indicate that EGCG attenuates the neurotoxicity in Alzheimer's disease (AD) via a novel mechanism that involves inhibition of ER-stress-associated neuronal apoptosis in vitro and in vivo, suggesting the tremendous potential of EGCG for use in a nutritional preventive strategy against AD.

Phycoerythrin-Derived Tryptic Peptide of a Red Alga Pyropia yezoensis Attenuates Glutamate-Induced ER Stress and Neuronal Senescence in Primary Rat Hippocampal Neurons.

SCOPE: Glutamate excitotoxicity has been observed in association with neurodegenerative disorders. This study aimed to investigate whether a phycoerythrin-derived tryptic peptide of Pyropia yezoensis (PYP) reduces glutamate-induced excitotoxicity and neuronal senescence in primary rat hippocampal neurons. METHODS AND RESULTS: Glutamate exposure (100 µm) decreased cell viability and increased expression of endoplasmic reticulum (ER) stress response protein glucose-regulated protein 78 (GRP78) starting at 60 min following glutamate exposure, which was prevented by pretreating the neurons with PYP (1 µg mL-1 ). The glutamate-induced increase in GRP78 expression was downregulated by blocking N-methyl-d-aspartate (NMDA) receptor with MK801 (10 µm) and inhibiting c-Jun N-terminal kinase (JNK) phosphorylation with SP600125 (10 µm). Moreover, phosphorylation of JNK was decreased by blockade of NMDA receptor. The PYP pretreatment downregulated glutamate-induced increase in GRP78 expression and JNK phosphorylation, and this effect was abolished by inhibiting tropomyosin-related kinase B (TrkB) receptor, phosphatidylinositiol 3-kinase, and extracellular signal-regulated kinase (ERK)1/2 using cyclotraxin B (200 nm), LY294002 (20 µm), and SL327 (10 µm), respectively. In addition, PYP downregulated increase in GRP78 expression, senescence-associated ß-galactosidase activity, and neurite degeneration in aging hippocampal neurons. CONCLUSION: These findings indicate that activation of TrkB receptor-mediated ERK1/2 by PYP attenuates glutamate-induced ER stress, which may improve the survival of hippocampal neurons with age.

Gamma-linolenic acid ameliorated glycation-induced memory impairment in rats.

CONTEXT: γ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements. OBJECTIVE: The current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats. MATERIALS AND METHODS: GLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 µM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs) in vitro. For in vivo assessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed using d-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina. RESULTS: Our data showed that GLA inhibited the production of AGEs (IC50 = 1.12 ± 0.05 µM). However, this effect was more significant at lower tested doses. A similar pattern was also observed in in vivo experiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). The in silico data exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE. CONCLUSION: The GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline.

Natural product-based amyloid inhibitors.

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned.

The protective role of plant biophenols in mechanisms of Alzheimer's disease.

Self-assembly of amyloid beta peptide (Aß) into the neurotoxic oligomers followed by fibrillar aggregates is a defining characteristic of Alzheimer's disease (AD). Several lines of proposed hypotheses have suggested the mechanism of AD pathology, though the exact pathophysiological mechanism is not yet elucidated. The poor understanding of AD and multitude of adverse responses reported from the current synthetic drugs are the leading cause of failure in the drug development to treat or halt the progression of AD and mandate the search for safer and more efficient alternatives. A number of natural compounds have shown the ability to prevent the formation of the toxic oligomers and disrupt the aggregates, thus attracted much attention. Referable to the abundancy and multitude of pharmacological activities of the plant active constituents, biophenols that distinguish them from the other phytochemicals as a natural weapon against the neurodegenerative disorders. This review provides a critical assessment of the current literature on in vitro and in vivo mechanistic activities of biophenols associated with the prevention and treatment of AD. We have contended the need for more comprehensive approaches to evaluate the anti-AD activity of biophenols at various pathologic levels and to assess the current evidences. Consequently, we highlighted the various problems and challenges confronting the AD research, and offer recommendations for future research.

Efectos positivos del entrenamiento de karate en las capacidades cognitivas asociadas a la edad / Possitive effects of continuous practice of karate in cognitive capacity associtated to the age

El envejecimiento está asociado con la disminución de las capacidades cognitivas de las personas y, en muchos casos, va acompañado de un descenso de la calidad de vida. El objetivo de este trabajo de investigación consiste en identificar los efectos que un entrenamiento adaptado y continuado en karate puede tener en las capacidades cognitivas de personas de más de cuarenta años. Para ello se obtuvo una muestra incidental de 275 sujetos. Se llevó a cabo un trabajo empírico descriptivo y correlacional. La variable investigada es la velocidad de anticipación, medida mediante la puntuación obtenida en el test Kelvin (KCC). Las variables controladas son la edad, sexo y la práctica continuada de karate. El entrenamiento regular en karate ha tenido efectos positivos en la velocidad de anticipación de las personas mayores de cuarenta años, lo que implica una mejora en la atención y otras capacidades cognitivas de estas personas. En los sujetos no practicantes de Karate, al llevar a cabo la comparación de medias entre mayores y menores de 40 años, sí se han encontrado diferencias significativas. Por tanto, el entrenamiento adaptado de karate puede ser una opción interesante para mantener las capacidades cognitivas a lo largo de los procesos envejecimiento (AU)

Normally, aging has been associated to the decrease of people’s cognitive capacity and, in several cases, related to a decrease in the quality of life. The objective of this research work is the identification of the effects that an adapted and continuous practice of karate would have in the cognitive capacity of people having more than 40 years old. To achieve this aim, 275 subjects were analysed through an empirical and correlational approach. The dependent variable analysed was the anticipation speed measured by he points obtained by the participants in the Kelvin test (KCC). The independent variables considered were age, gender and the continuous practice of karate. The results obtained indicate that the regular and adapted karate training have positive effects in the anticipation speed of people having more than 40 years old. In this group the anticipation speed has not relevant differences between people having less and more than 40 years old. There were relevant differences between both subsets in the case of subjects that were not karate practitioners. In this sense, the continuous practice of karate could be an interesting option to maintain the cognitive capacities throughout aging processes (AU)

Homocysteine, B Vitamins, and Cognitive Impairment.

Moderately elevated plasma total homocysteine (tHcy) is a strong modifiable risk factor for vascular dementia and Alzheimer's disease. Prospectively, elevated tHcy is associated with cognitive decline, white matter damage, brain atrophy, neurofibrillary tangles, and dementia. Most homocysteine-lowering trials with folate and vitamins B6 and/or B12 tested as protective agents against cognitive decline were poorly designed by including subjects unlikely to benefit during the trial period. In contrast, trials in high-risk subjects, which have taken into account the baseline B vitamin status, show a slowing of cognitive decline and of atrophy in critical brain regions, results that are consistent with modification of the Alzheimer's disease process. Homocysteine may interact with both risk factors and protective factors, thereby identifying people at risk but also providing potential strategies for early intervention. Public health steps to slow cognitive decline should be promoted in individuals who are at risk of dementia, and more trials are needed to see if simple interventions with nutrients can prevent progression to dementia.

Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women.

Common pharmacological treatments of mood disorders aim to modulate serotonergic neurotransmission and enhance serotonin levels in the brain. Brain serotonin levels are dependent on the availability of its food-derived precursor essential amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via food may serve as an alternative treatment, and examined the effects of a Trp-rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive and emotional functions, mood state, and sleep quality. In a randomised, placebo-controlled, parallel trial, fifty-nine mentally and physically healthy women aged 45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice per d) for 19 d. Emotional processing was significantly changed by supplementation, exhibiting a shift in bias away from negative stimuli. The results for the Affective Go/No-Go Task exhibited a slowing of responses to negative words, suggesting reduced attention to negative emotional stimuli. The results for the Facial Emotional Expression Rating Task also supported a shift away from attention to negative emotions and a bias towards happiness. An increase in arousal-like symptoms, labelled 'high energy', shorter reaction times and a slight benefit to sustained attention were observed in the treated subjects. Finally, when the supplement was taken 60-90 min before bedtime, a feeling of happiness before going to bed was consistently reported. In summary, daily consumption of a low-dose supplement containing bioavailable Trp may have beneficial effects on emotional and cognitive functions.

Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans.

Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status.

Rats given linseed oil in microemulsion forms enriches the brain synaptic membrane with docosahexaenoic acid and enhances the neurotransmitter levels in the brain.

Long chain n-3 fatty acids such as docosahexaenoic acid (DHA) are essential for the normal functioning of the brain. The vegetarian sections of the population get only alpha-linolenic acid (ALA) through their diet as a source of n-3 fatty acids. Hence, in this group of the population, the ALAs need to be converted to DHA through the action of the desaturase and the elongase enzymes. However, the conversion of the ALA to the DHA is very minimal (<2%) in mammals. Our recent studies have shown that the conversion of the ALA to the DHA can be enhanced significantly when given in the microemulsion forms. This work was undertaken to study the feasibility of enriching the synaptic membranes of rat brain with the DHA by providing the microemulsions of linseed oil (LSO) containing ALA. The rats were fed LSO as microemulsions in whey protein or in lipoid for 60 days through gavage. The rats given LSO microemulsions in lipoid showed higher levels of the DHA in the brain synaptic membrane when compared to rats given LSO without emulsion formation. This decreased the n-6/n-3 fatty acid ratio of the brain synaptic membrane. This also increased the membrane fluidity, Na⁺-K⁺ ATPase activity, and acetylcholine esterase activity in the synaptic membranes. Furthermore, Ca²âº-Mg²âº ATPase activity, monoamine oxidase A and monoamine oxidase B activity was lowered in the rats given LSO in the microemulsion form. The dopamine and the serotonin levels in the brain were increased in the rats given LSO in the microemulsion form with lipoid as compared to those given LSO without the preemulsion formation. This study indicates that the LSO microemulsions in the lipoid can enhance the synaptic membrane DHA levels and influence the functions associated with the brain in a beneficial manner.

Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation.

Previous research has shown that resveratrol can increase cerebral blood flow (CBF) in the absence of improved cognitive performance in healthy, young human subjects during the performance of cognitively demanding tasks. This lack of cognitive effects may be due to low bioavailability and, in turn, reduced bioefficacy of resveratrol in vivo. Piperine can alter polyphenol pharmacokinetics, but previous studies have not investigated whether this affects the efficacy of the target compound. Therefore, the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF. The present study utilised a randomised, double-blind, placebo-controlled, within-subjects design, where twenty-three adults were given placebo, trans-resveratrol (250 mg) and trans-resveratrol with 20 mg piperine on separate days at least a week apart. After a 40 min rest/absorption period, the participants performed a selection of cognitive tasks and CBF was assessed throughout the period, in the frontal cortex, using near-IR spectroscopy. The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort (n 6). The results indicated that when co-supplemented, piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone. Cognitive function, mood and blood pressure were not affected. The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments, which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects, but not cognitive performance, and does this without altering bioavailability.

Trace metals accumulation in Bacopa monnieri and their bioaccessibility.

Bacopa monnieri is commonly known as "Brahmi" or "Water hyssop" and is a source of nootropic drugs. Aboveground parts of plant samples collected from peri-urban Indian areas were analysed for total trace metal concentrations. Subsequently, three samples with high concentrations of Cd and Pb were subjected to in vitro gastrointestinal digestion to assess the bioaccessibility of the trace metals in these plants. The total concentrations of trace metals on a dry weight basis were 1.3 to 6.7 mg·kg⁻¹ Cd, 1.5 to 22 mg·kg⁻¹ Pb, 36 to 237 mg·kg⁻¹ Cu, and 78 to 186 mg·kg⁻¹ Zn. The majority of Bacopa monnieri samples exceeded threshold limits of Cd, Pb, Cu, and Zn for use as raw medicinal plant material or direct consumption. Therefore, it is necessary to evaluate Bacopa monnieri collected in nature for their trace metal content prior to human consumption and preparation of herbal formulations.

Long-lasting effects of prenatal dietary choline availability on object recognition memory ability in adult rats.

Choline is an essential nutrient required for early development. Previous studies have shown that prenatal choline availability influences adult memory abilities depending on the medial temporal lobe integrity. The relevance of prenatal choline availability on object recognition memory was assessed in adult Wistar rats. Three groups of pregnant Wistar rats were fed from E12 to E18 with choline-deficient (0 g/kg choline chloride), standard (1.1 g/kg choline chloride), or choline-supplemented (5 g/kg choline chloride) diets. The offspring was cross-fostered to rat dams fed a standard diet during pregnancy and tested at the age of 3 months in an object recognition memory task applying retention tests 24 and 48 hours after acquisition. Although no significant differences have been found in the performance of the three groups during the first retention test, the supplemented group exhibited improved memory compared with both the standard and the deficient group in the second retention test, 48 hours after acquisition. In addition, at the second retention test the deficient group did not differ from chance. Taken together, the results support the notion of a long-lasting beneficial effect of prenatal choline supplementation on object recognition memory which is evident when the rats reach adulthood. The results are discussed in terms of their relevance for improving the understanding of the cholinergic involvement in object recognition memory and the implications of the importance of maternal diet for lifelong cognitive abilities.

Stimulation of mild, sustained ketonemia by medium-chain triacylglycerols in healthy humans: estimated potential contribution to brain energy metabolism.

OBJECTIVE: In humans consuming a normal diet, we investigated 1) the capacity of a medium-chain triacylglycerol (MCT) supplement to stimulate and sustain ketonemia, 2) ¹³C-ß-hydroxybutyrate and ¹³C-trioctanoate metabolism, and 3) the theoretical contribution of the degree of ketonemia achieved to brain energy metabolism. METHODS: Eight healthy adults (26 ± 1 y old) were given an MCT supplement for 4 wk (4 times/d; total of 20 g/d for 1 wk followed by 30 g/d for 3 wk). Ketones, glucose, triacylglycerols, cholesterol, free fatty acids, and insulin were measured over 8 h during two separate metabolic study days before and after MCT supplementation. Using isotope ratio mass spectroscopy, ¹³C-D-ß-hydroxybutyrate and ¹³C-trioctanoate ß-oxidation to ¹³CO2 was measured over 12 h on the pre- and post-MCT metabolic study days. RESULTS: On the post-MCT metabolic study day, plasma ketones (ß-hydroxybutyrate plus acetoacetate) peaked at 476 µM, with a mean value throughout the study day of 290 µM. Post-MCT, ¹³C-trioctanoate ß-oxidation was significantly lower 1 to 8 h later but higher 10 to 12 h later. MCT supplementation did not significantly alter ¹³C-D-ß-hydroxybutyrate oxidation. CONCLUSIONS: This MCT supplementation protocol was mildly and safely ketogenic and had no side effects in healthy humans on their regular diet. This degree of ketonemia is estimated to contribute up to 8% to 9% of brain energy metabolism.

The effect of caffeine on working memory load-related brain activation in middle-aged males.

Caffeine is commonly consumed in an effort to enhance cognitive performance. However, little is known about the usefulness of caffeine with regard to memory enhancement, with previous studies showing inconsistent effects on memory performance. We aimed to determine the effect of caffeine on working memory (WM) load-related activation during encoding, maintenance and retrieval phases of a WM maintenance task using functional magnetic resonance imaging (fMRI). 20 healthy, male, habitual caffeine consumers aged 40-61 years were administered 100 mg of caffeine in a double-blind placebo-controlled crossover design. Participants were scanned in a non-withdrawn state following a workday during which caffeinated products were consumed according to individual normal use (range = 145-595 mg). Acute caffeine administration was associated with increased load-related activation compared to placebo in the left and right dorsolateral prefrontal cortex during WM encoding, but decreased load-related activation in the left thalamus during WM maintenance. These findings are indicative of an effect of caffeine on the fronto-parietal network involved in the top-down cognitive control of WM processes during encoding and an effect on the prefrontal cortico-thalamic loop involved in the interaction between arousal and the top-down control of attention during maintenance. Therefore, the effects of caffeine on WM may be attributed to both a direct effect of caffeine on WM processes, as well as an indirect effect on WM via arousal modulation. Behavioural and fMRI results were more consistent with a detrimental effect of caffeine on WM at higher levels of WM load, than caffeine-related WM enhancement. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Supplementation with DHA and the psychological functioning of young adults.

The grey matter of the brain contains high levels of the essential nutrient DHA. Although the role of DHA in the developing brain and in dementia has attracted attention, its influence on the brain of the healthy adult has been little considered. A total of 285 young adult females took 400 mg of DHA, in a double-blind, placebo-controlled trial, for 50 d. After 50 d, recently acquired information was more likely to be forgotten by those who had consumed DHA. No significant differences in mood, reaction times, vigilance or visual acuity were found.

Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies.

Omega-(n)-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions, from modulating synaptic plasticity and neurochemistry, to neuroimmune-modulation and neuroprotection. Thus, it is not surprising that n-3 PUFA are widely acknowledged to have cognitive-enhancing effects. Although clinical evidence is somewhat conflicting, probably in large part due to methodological issues, animal studies have consistently demonstrated that n-3 PUFA are indispensable for proper brain development, may enhance cognitive function in healthy, adult individuals and attenuate cognitive impairment in aging and age-related disorders, such as dementia. This review discusses and integrates up to date evidence from clinical and animal studies investigating the cognitive-enhancing effects of n-3 PUFA during development, child- and adult-hood, as well as old-age with associated neurodegenerative diseases, such as Alzheimer's disease. Furthermore, we cover the major underlying biochemical and neurophysiological mechanisms by which n-3 PUFA mediate these effects on cognition. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats.

BACKGROUND & OBJECTIVES: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. METHODS: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. RESULTS: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. INTERPRETATION & CONCLUSIONS: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats.