Nootropic Activity Research Articles

LIGNANS FROM SHIZANDRA CHINENSIS SEMINA OLEUM EXTRACT

was realized in “cruciform raised labyrinth” (CRl). The labyrinth installation was central square area (10c10 cm) with four “corridors” (boards with width of 10 cm and length of 50 cm) that moved off from every wall. Two of them oppositely placed “closed corridors” were limited on sides to walls that height of which was 40 cm, two ones were “opened corridors” that were without any walls. The installation was raised at a height of 50 cm above floor level and was illuminated from one side by a lamp with power of 50 W. A rat was placed on a central area so that their muzzles were against opened corridor. After that number of visits in closed and opened corridors and general time, that a rat was there, were registered. Every animal was been supervised for 5 minutes. On the 8 th day of the experiment method of conditioned reaction of passive avoidance was used: animals were tough in the installation that had light and dark compartments with electrode floor. The compartments were divided by partition with hole of a wire 4 cm. in diameter stretch. Animal was placed in light compartment and after its movement in dark compartment; electric painful irritation was provoked by series of switching on current in electrode floor with power of 1,5 mA during 1 sec in 2 sec. Thereby reflex of “dark compartment” was formed. Nootropic activity of test drug was estimated according to duration of latent period (safety of memorial track) up to animal’s movement from light to dark compartment of installation in 1,3 and 7 twenty-four hours after teaching. in test

THE STUDy OF THE NEUROPSyCHOPHARMACOLOGICAL EFFECTS OF THE NEW DERIVATIVE OF GLUTAMIC ACID, THE RGPU-197 COMPOUND

Proceeding from the proposition about the high productivity of the search of neuropsychotropic substances among the derivatives of natural neuromediators, a study of neuropsychopharmacological effects of the derivative of the glutamic acid, RGPU-197 compound was carried out. The study was carried out on the he-rats of the Wistar line using the following tests: “open field”, elevated plus maze, conditioned passive-avoidance response, the test of extrapolational deliverance, the test of hanging mice by tails; and also the methods of statistic analysis: rank univariate analysis of Cruscal-Wallace, the Dunn multiple comparison test /the multiple comparison test of Dunn, the x2 criterion. The RGPU-197 compound significantly (p<0,05, p<0,01) decreases the duration of immobilization of the animals and expands the latent period of its approach in the test of hanging mice by tails — it possesses antidepressant activity; increases the quantity of the visits of the centre of the open field, the quantity of attendings of the open hoses of elevated plus maze and the time of stay in them — it shows anxiolytic action; increases the quantity of crossed squares in the open field and the quantity of crossings between the hoses of elevated plus maze — it possesses activating effect; during the displays of the avoidance reflex it expands the latent period of the first period of entering the dark compartment and the quantity of enterings of it in conditioned passive-avoidance response, reduces the latent period of diving under in the test of extrapolational deliverance — it shows nootropic action. According to the intensity of antidepressant action RGPU-197 doesn’t yield to melipramin, anxiolytic and activating effects significantly (p<0.05) excels phenibutum and doesn’t yield to it by nootropic activity. Thus, the new derivative of glutamate, the RGPU-197 compound, possesses the marked antidepressant, anxiolytic and activating effects, as well as nootropic activity.

The Nootropic and Analgesic Effects of Semax Given via Different Routes

The heptapeptide Semax (MEHFPGP) is an analog of the fragment ACTH(4–10) with long-lasting actions. The aim of the present work was to study the effects of Semax on learning ability and pain sensitivity in white rats given different doses via the intraperitoneal and intranasal routes. The nootropic effects of Semax were studied in a test based on the acquisition of a conditioned passive avoidance reaction to pain stimulation. Pain sensitivity was assessed in a hindpaw compression test. The results showed that i.p. Semax had nootropic and analgesic actions. Dose-response characteristics were different for these different effects. Intranasal Semax was more effective in improving learning in animals than i.p. Semax but had no effect on pain sensitivity. Our results provide evidence that different mechanisms and brain structures are involved in mediating the nootropic and analgesic effects of Semax.

Influence of ring size on the cognition-enhancing activity of DM235 and MN19, two potent nootropic drugs

A series of analogs of DM235 and MN19, characterized by rings with different size, have been prepared and evaluated for their nootropic activity in the mouse passive-avoidance test. It was found that the optimal ring size for the analogs of DM235, showing endocyclic both amidic groups, is 6 or 7 atoms. For the compounds structurally related to MN19, carrying an exocyclic amide group, the piperidine ring is the moiety which gives the most interesting compounds.

Effect of leaf extract of Capparis zeylanica Linn. on spatial learning and memory in rats

This study was designed to investigate the nootropic activity of Capparis zeylanica Linn. leaves in rats. The raw material of Capparis zeylanica leaves was successively extracted with petroleum ether and methanol using a Soxhlet apparatus and macerated to form an aqueous extract. The methanolic and aqueous extracts were evaluated for their effect on spatial learning and memory in rats using the Morris water maze task. Three doses (50, 100 and 150mg/kg; p.o.) of methanolic and aqueous extracts of Capparis zeylanica were administered for 7 successive days to separate groups of animals. Results showed that both the extracts significantly enhanced memory, as shown by decrease in escape latency time. Furthermore, methanolic and aqueous extracts in all doses tested significantly increased the time spent in the target quadrant during the probe trial, indicating retention of spatial memory of the location of a previously placed platform in the target quadrant. These findings indicate that methanolic and aqueous extracts of Capparis zeylanica Linn. leaves have potent nootropic activity. The anti-oxidant property of Capparis zeylanica may contribute favorably to the memory enhancement effect. However, further studies are needed to identify the exact mechanism of action.

Nootropic action of some antihypertensive drugs: computer predicting and experimental testing

Several antihypertensive drugs belonging to the group of ACE inhibitors have been selected for testing their nootropic activity based on a computer-aided prediction of their biological activity spectra using the PASS computer program package. Experiments were conducted on mice by the spontaneous orientation test (patrolling behavior) in a cross-maze. It was found that perindopril at a dose of 1 mg/kg in addition to quinapril and monopril at a dose of 10 mg/kg improved the patrolling behavior in the cross-maze test. This effect is similar to the effects of the standard nootropic drugs piracetam and meclofenoxate (at doses of 300 and 120 mg/kg, respectively). The observed nootropic effect of some ACE inhibitors is likely to be unrelated to their antihypertensive effect since the nootropic action took place only at relatively low doses of perindopril, quinapril, and monopril and was not observed with further increase of the dose. The identification of nootropic action of antihypertensive drugs that are commonly used in clinical practice leads to their new clinical applications with allowance for the relevant idiosyncrasies of patients.

2,5-Diketopiperazines as Neuroprotective Agents

2,5-diketopiperazines are the simplest cyclic peptides found in nature, commonly biosynthesized from amino acids by different organisms, and represent a promising class of biologically active natural products. Their peculiar heterocyclic structure confers high stability against the proteolysis and constitutes a structural requirement for the active intestinal absorption. Furthermore, the diketopiperazine-based motif is considered as a novel brain shuttle for the delivery of drugs with limited ability to cross the blood-brain barrier (BBB) and can be proposed as an ideal candidate for the rational development of new therapeutic agents. Although these cyclic peptides have been known since the beginning of the 20th century, only recently have they attracted substantial interest with respect to the wide spectrum of their biological properties, including antitumor, antiviral, antifungal, antibacterial and antihyperglycemic activities. In addition to these, the most challenging function of the diketopiperazine derivatives is related with their remarkable neuroprotective and nootropic activity. The aim of the present paper is to provide an overview of the two major classes of diketopiperazines, the TRH-related and the unsaturated derivatives both characterized by a significant ability to protect against neurotoxicity in several experimental models. The neuroprotective profile of these compounds suggests that they may have a future utility in the therapy of neuronal degeneration in vivo, potentially through several different mechanisms.

Nootropic activity of acetaminophen against colchicine induced cognitive impairment in rats

Alzheimer’s disease is a devastating neurodegenerative disorder, the most common among the dementing illnesses. Acetaminophen has gaining importance in neurodegenerative diseases by attenuating the dopaminergic neurodegeneration in Caenorhabditis elegans model, decreasing the chemokines and the cytokines and increasing the anti apoptotic protein such as Bcl-2 in neuronal cell culture. The low concentration acetaminophen improved the facilitation to find the hidden platform in Morris Water Maze Test. Also some data suggest that acetaminophen could contribute in neurodegeneration. The present study was aimed to evaluate the effect of acetaminophen against colchicine induced cognitive impairment and oxidative stress in wistar rats. The cognitive learning and memory behaviour was assessed using step through passive avoidance paradigm and acetylcholine esterase activity. The parameters of oxidative stress were assessed by measuring the malondialdehyde, reduced glutathione and catalase levels in the whole brain homogenates. There was a significant memory improvement in the rats received acetaminophen treatment and it has also decreased the acetylcholine esterase enzyme level, confirming its nootropic activity. Acetaminophen neither increases nor decreases the reduced glutathione and catalase in the whole brain homogenates, showing that acetaminophen is devoid of any adverse effect on brain antioxidant defense system.

Nootropic herbs (Medhya Rasayana) in Ayurveda: An update

Cognitive deficits that present with many of neuropsychiatric conditions and/or alone as developmental deficit demand use of nootropics to boost cognitive abilities. Recently there is a tremendous urge to explore medicinal plants globally for improving cognitive function owing to their less adverse effects. Ayurveda provides a list of herbs known for nootropic activity as well as their multi-dimensional utility in various conditions. Present paper is a review to update knowledge on pharmacological properties, major chemical constituents, therapeutic actions, preclinical studies, safety and possible mode of action of the selected herbs from ayurvedic pharmacopoeia. Concurrently, it opens up for further research and standardization on nootropic herbs

Binding Profiles of a Series of 2-Arylpropionic Acid Esters on Cloned Human Muscarinic Receptor Subtypes (m1-m5) and Their Relationship to Nootropic Activity

The muscarinic binding profile of a series of 2-arylpropionic acid esters on cloned human muscarinic receptor subtypes (m1-m5) was determined to investigate whether there is a correlation between pharmacological activity and muscarinic receptor subtype selectivity. Among the tested compounds, 1, 7 and 9 showed the highest affinity for the m2 and m4 receptors. Compounds 1, 7 and 9 show good affinity for m4 receptors (pKi = 7.87; 7.73 and 7.10, respectively) and are able to discriminate 10-60 fold between m4/m1, m4/m3, and m4/m5 subtypes. Conversely, these compounds are able only to weakly discriminate between m4/m2. Compounds 1 (50-300 micrograms kg-1 i.p.) and 7 (1-10 micrograms kg-1 i.p.), injected 20 min before the training session, are able to prevent the amnesia induced by dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Compounds 1 and 7, at the highest antiamnesic doses, do not modify motor coordination and spontaneous motility as evaluated by the rota-rod test and Animex apparatus experiments.

Cognition boosting effect of Canscora decussata (a South Indian Shankhpushpi)

Aim of the studyIn southern India, ayurvedic practitioners traditionally employ the whole herb of Canscora decussata Schult. (CD) (Gentianaceae) as a traditional ayruvedic medicine, Shankhpushpi for its memory potentiating, anxiolytic and tranquilizing properties. The present study investigated the effect of CD, which is regarded as Shankhpushpi, for its effects on learning and memory in rodents. The extract was further studied for its in vitro acetylcholinesterase (AChE) inhibitory potential which can correlate with its cognition boosting effect. Materials and methodsEthanol extract of CD was analyzed by high performance thin layer chromatography (HPTLC) and high performance liquid chromatography (HPLC). Ethanol extract of CD was investigated for its AChE enzyme inhibitory activity. Nootropic activity using Elevated plus maze apparatus, passive avoidance (Cook and Weidley's pole climbing, step down) paradigms and active avoidance (two compartment shuttle box) test were used to learning and memory. ResultsHPTLC and HPLC fingerprinting of ethanol extract revealed presence of mangiferin as its main constituent. It was found that CD potentially inhibits AChE with 50% inhibitory concentration (IC50) of 165.667±0.213μg/ml. It was found that groups (n=6), receiving ethanol extract in doses of 200 and 400mg/kg p.o. significantly reversed the amnesia induced by scopolamine (0.3mg/kg i.p.). Nootropic activity was compared using piracetam (100mg/kg p.o.) as the standard. ConclusionEthanol extract of CD showed significant effects on learning behavior and memory enhancement as evidenced from the experiments performed. The activity may be attributed to the presence of various xanthones and mangiferin, a polyphenolic xanthone.

Effects of Walnuts (Juglans regia) on Learning and Memory Functions

Walnut has been regarded as a health food that is delicious and nutritious. Both preventive and therapeutic effects of walnut are well documented. Walnuts are rich in omega-3 fatty acids that are reported to have beneficial effects on brain function. The present work was designed to evaluate the effects of walnuts on learning and memory in male rats. The effect of oral intake of walnut was also monitored on food intake. Walnut was given orally to rats for a period of 28days. Memory function in rats was assessed by elevated plus maze (EPM) and radial arm maze (RAM). A significant improvement in learning and memory of walnut treated rats compared to controls was observed. Walnut treated rats also exhibited a significant decrease in food intake while the change in growth rate (in terms of percentage) remained comparable between the two groups. Analysis of brain monoamines exhibited enhanced serotonergic levels in rat brain following oral intake of walnuts. The findings suggest that walnut may exert its hypophagic and nootropic actions via an enhancement of brain 5-HT metabolism.

Genes targets identification of 5-amino-exo-3-azatricyclo[5.2.1.02,6]decane-4-one in an in vivo model of arrhythmia

The goal of the current work is to study the molecular mechanisms underlay the action of 5- amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one (P-11) with combined antiarrhythmic, nootropic, anti-inflammatory and anaesthetic activities. The aconitine-induced experimental rat model of cardiac arrhythmia has been used in our study. Aconitine was administered once intravenously in a dose 50 microg/kg whereas experimental animal group received P-11 in a dose 0.3 mg/kg (the compound was injected intravenously 2 min before acute aconitine treatment). Expression macroarray (Atlas Rat cDNA Expression Array, #7738-1; BD Biosciences) was used to identify the target genes for P-11 compound. Comparative analysis of changes in the status of expression of genes in the heart of rats induced by P-11 against the simulated in vivo arrhythmia identified 16 genes that reproducibly alter the level of expression.These genes encode the extracellular matrix proteins (glypican 1, Gpc1; tissue inhibitor of metalloproteinase 2, 3, Timp2, Timp 3); intracellular signaling molecules (rho GTPase activating protein 7, Dlc1; protein tyrosine phosphatase 4a1, Ptp4a1; phosphodiesterase 4D, PDE4D; PI3-kinase regulatory subunit alpha, PIK3R1; guanine nucleotide binding protein alpha 12, Gna12) and protein of intermediate junctions (junction plakoglobin, Jup), proteins involved in glycolysis (phosphofructokinase I, Pfk1) and hemostasis (tissue plasminogen activator, Plat), plasma membrane transporters (Solute carrier family 16, member 1, Slc16a1; ATPase, Na+/K+ transporting, Atp1a), and ets. (c-fos protooncogene, c-fos; telomerase protein component 1, tlp; Annexin 1, anxa 1). Thus, the data about the selective effect of P-11 on genes whose products are involved in the aritmogenesys mechanisms, allow us to consider this compound as a promising means of pathogenetically oriented pharmacotherapy of cardiac arrhythmias.

Amino-acid composition and nootropic properties of polynoophyt

The nootropic activity of the complex plant preparation polynoophyt (polynoofyt) has been established in animal experiments. The amino-acid composition of the phytopreparation has been studied. A total of 19 amino acids including seven essential ones was identified. The most significant concentrations were found for aspargic acid, asparagine, glutamic acid, glutamine, proline, cystine, methionine, leucine, γ-aminobutyric acid, alanine, and arginine.

Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi

Context: Shankhpushpi, a well-known drug in Ayurveda, is extensively used for different central nervous system (CNS) effects especially memory enhancement. Different plants are used under the name shankhpushpi in different regions of India, leading to an uncertainty regarding its true source. Plants commonly used under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn. (Leguminosae).Objective: To find out the true source of shankhpushpi by evaluating and comparing memory-enhancing activity of the three above mentioned plants. Anxiolytic, antidepressant and CNS-depressant activities of these three plants were also compared and evaluated.Materials and methods: The nootropic activity of the aqueous methanol extract of each plant was tested using elevated plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS-depressant studies were evaluated using EPM, Porsolt’s swim despair and actophotometer models, respectively.Results: C. pluricaulis extract (CPE) at a dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p < 0.001). E. alsinoides extract (EAE) and C. ternatea extract (CTE) showed maximum memory-enhancing and anxiolytic activity (p < 0.001) at 200 and 100 mg/kg, respectively. Amongst the three plants, EAE and CTE showed significant (p < 0.05), while CPE did not exhibit any antidepressant activity. All the three plants showed CNS-depressant action at higher dose levels.Discussion and conclusions: The above results showed all the three plants possess nootropic, anxiolytic and CNS-depressant activity. The results of memory-enhancing activity suggest C. pluricaulis to be used as true source of shankhpushpi.

PASS assisted prediction and pharmacological evaluation of novel nicotinic analogs for nootropic activity in mice

The aim of present study is to predict the probable nootropic activity of novel nicotine analogues with the help of computer program, PASS (prediction of activity spectra for substances) and evaluate the same. Two compounds from differently substituted pyridines were selected for synthesis and evaluation of nootropic activity based on their high probable activity (Pa) value predicted by PASS computer program. Evaluation of nootropic activity of compounds after acute and chronic treatment was done with transfer latency (TL) and step down latency (SDL) methods which showed significant nootropic activity. The effect on scopolamine induced amnesia was also observed along with their acetylcholine esterase inhibitory activity which also showed positive results which strengthened their efficacy as nootropic agents through involvement of cholinergic system. This nootropic effect was similar to the effect of nicotine and donepezil used as standard drugs. Muscle coordination and locomotor activity along with their addiction liability, safety and tolerability studies were also evaluated. These studies showed that these compounds are well tolerable and safe over a wide range of doses tested along with the absence of withdrawal effect which is present in nicotine due to its addiction liability. The study showed that these compounds are true nicotine analogs with desirable efficacy and safety profile for their use as effective nootropic agents.

Synthesis and Biological Evaluation of 3,7-Diazabicyclo[4.3.0]nonan-8-ones as Potential Nootropic and Analgesic Drugs

A series of cis and trans 3,7-diazabicyclo[4.3.0]nonan-8-ones has been synthesized and tested for their ability to revert scopolamine-induced amnesia in the mouse passive-avoidance test. The racemates of the most potent compounds 4 and 7 were separated and tested, but no enantioselectivity was found for the nootropic activity. Compounds 4 and 7 and their enantiomers displayed interesting antihyperalgesic activity in two models of neuropathic pain (streptozotocin-induced and oxalilplatin-induced neuropathy) in comparison with pregabalin.

P03-81 - Cognition improving effects of clerodendron phlomidis linn. bark extract in mice

Normal ageing is known to deteriorate memory in human beings. Oxygen free radicals, the harmful byproducts of oxidative metabolism are known to cause organic damage to the living system, which may be responsible for the development of Alzheimer's disease in elderly. Clerodendron phlomidis Linn. (Verbenaceae) is known as Agnimantha in sanskrit. Bark of the plant is used in treating various nervous disorders. In the present study C. phlomidis was investigated for its potential as a nootropic agent in mice. The aqueous extract of the C. phlomidis (100 and 200 mg/kg, p.o.) was administered for 6 successive days to both young and aged mice. Exteroceptive behavioral models such as elevated plus maze and passive avoidance paradigm were employed to evaluate short term and long term memory respectively. Scopolamine, diazepam were used to induce amnesia in mice. To delineate the mechanism by which C. phlomidis exerts nootropic action, its effect on brain acetyl cholinesterase levels were determined. Piracetam was used as a standard nootropic agent. Pretreatment with C. phlomidis (100 and 200 mg/kg, p.o.) for 6 successive days significantly improved learning and memory in mice. It reversed the amnesia induced by scopolamine, diazepam and natural ageing. It also decreased the acetyl cholinesterase levels in the whole brain. The bark of C. phlomidis can be useful in treatment of cognitive disorders such as amnesia and Alzheimer's disease.

Synthesis and biological evaluation of Schiff’s bases and 2-azetidinones of isonocotinyl hydrazone as potential antidepressant and nootropic agents

The synthesis and pharmacological activity of N′-[(1Z)-(substituted aromatic) methylidene] pyridine-4-carbohydrazides (3a–k) and N-[3-chloro-2-(substituted aromatic)-4-oxoazetidin-1-yl]pyridine-4-carboxamides (5a–k) are described. Synthesis of 2-azetidinones was performed by novel methods of stirring and sonication involving the cyclocondensation of the appropriate Schiff’s bases (3a–k) with chloroacetyl chloride, followed by the addition of triethyl amine in the presence of molecular sieves. The compounds were investigated for their antidepressant activity, compounds N′-[(1Z)-(2,5-dimethoxyphenyl)methylidene]pyridine-4-carbohydrazide (3k) and N-[3-chloro-2-(2,5-dimethoxyphenyl)-4-oxoazetidin-1-yl]pyridine-4-carboxamide (5k) with 2,5-dimethoxy substitution on the aryl ring exhibited the highest antidepressant activity. In the elevated plus maze test and passive avoidance test in mice for the evaluation of nootropic activity N′-[(1Z)-(4-nitrophenyl)methylidene]pyridine-4-carbohydrazide (3d) and N-[3-chloro-2-(4-nitrophenyl)-4-oxoazetidin-1-yl]pyridine-4-carboxamide (5d) with para nitro substitution on the aryl ring exhibited the highest activity. All synthesised Schiff’s bases and azetidinone analogues exhibited antidepressant and nootropic activities in a dose dependant manner. The results confirmed the fact that the 2-azetidinone skeleton has potential as a CNS active agent and can be explored for the development of more potent and safe CNS active agents for therapeutic use.

Exploring the Role of "Brahmi" (Bacopa monnieri and Centella asiatica) in Brain Function and Therapy

It has been envisaged that in this century, disorders of the central nervous system will have a significant bearing on the healthcare concerns of the human population worldwide. Such neurological and psychiatric disorders are generally associated with loss of memory, cognitive deficits, impaired mental function etc. Due to the multi-factorial nature of these diseases, modern medicine based psychoactive drugs have met with limited success. Therefore, there is a growing demand for novel products that could target multiple pathways and improve the mental capabilities either independently or in combination with conventional drugs. In the recent times, herbal products based on traditional knowledge have been increasingly used both in developed and developing countries. According to "Ayurveda", the Indian traditional system of medicine, "medhyarasayanas" represent herbal therapeutics that boost memory, restore cognitive deficits and improve mental function. The current review deals with the components and application of such a traditional herb "Brahmi" that corresponds to two plants, Bacopa monnieri and Centella asiatica. Research evidences clearly indicate that both plants possess neuroprotective properties, have nootropic activity with therapeutic implications for patients with memory loss. The field has witnessed exciting patent activity with most inventions aiming at either (i) improving the methods of herbal extraction or (ii) enrichment and purification of novel compounds from brahmi or (iii) providing novel synergistic formulations for therapeutics in various human ailments. In this review, clinical trials related to the therapeutic properties of brahmi and current patents relevant to the preparation, composition and application have also been included.