MSK1 is required for the experience- and ampakine-dependent enhancement of spatial reference memory and reversal learning and for the induction of Arc and BDNF.

There is considerable interest in the development of nootropics, pharmacological agents that can improve cognition across a range of both cognitive modalities and cognitive disabilities. One class of cognitive enhancers, the ampakines, has attracted particular attention by virtue of improving cognition associated with animal models of neurodevelopmental, neurodegenerative, and psychiatric conditions, as well as in age-related cognitive impairment. Ampakines elevate CNS levels of BDNF, and it is through this elevation that their beneficial actions are believed to occur. However, what transduces the elevation of BDNF into long-lasting cognitive enhancement is not known. We have previously shown that MSK1, by virtue of its ability to regulate gene transcription, converts the elevation of BDNF associated with environmental enrichment into molecular, synaptic, cognitive and genomic adaptations that underlie enrichment-induced enhanced synaptic plasticity and learning and memory, a property that MSK1 retains across the lifespan. To establish whether MSK1 similarly converts ampakine-induced elevations of BDNF into cognitive enhancement we tested an ampakine (CX929) in male WT mice and in male mice in which the kinase activity of MSK1 was inactivated. We found that MSK1 is required for the ampakine-dependent improvement in spatial reference memory and cognitive flexibility, and for the elevations of BDNF and the plasticity-related protein Arc associated with ampakines and experience. These observations implicate MSK1 as a key enabler of the beneficial effects of ampakines on cognitive function, and furthermore identify MSK1 as a hub for BDNF-elevating nootropic strategies.

Acute and Repeated Ashwagandha Supplementation Improves Markers of Cognitive Function and Mood.

BACKGROUND: Ashwagandha has been reported to reduce stress and attenuate cognitive decline associated with inflammation and neurodegeneration in clinical populations. However, the effects as a potential nootropic nutrient in younger populations are unclear. This study examined the effects of liposomal ashwagandha supplementation on cognitive function, mood, and markers of health and safety in healthy young men and women. METHODS: 59 men and women (22.7 ± 7 yrs., 74.9 ± 16 kg, 26.2 ± 5 BMI) fasted for 12 h, donated a fasting blood sample, and were administered the COMPASS cognitive function test battery (Word Recall, Word recognition, Choice Reaction Time Task, Picture Recognition, Digit Vigilance Task, Corsi Block test, Stroop test) and profile of mood states (POMS). In a randomized and double-blind manner, participants were administered 225 mg of a placebo (Gum Arabic) or ashwagandha (Withania somnifera) root and leaf extract coated with a liposomal covering. After 60-min, participants repeated cognitive assessments. Participants continued supplementation (225 mg/d) for 30 days and then returned to the lab to repeat the experiment. Data were analyzed using a general linear model (GLM) univariate analysis with repeated measures and pairwise comparisons of mean changes from baseline with 95% confidence intervals (CI). RESULTS: Ashwagandha supplementation improved acute and/or 30-day measures of Word Recall (correct and recalled attempts), Choice Reaction Time (targets identified), Picture Recognition ("yes" correct responses, correct and overall reaction time), Digit Vigilance (correct reaction time), Stroop Color-Word (congruent words identified, reaction time), and POMS (tension and fatigue) from baseline more consistently with several differences observed between groups. CONCLUSION: Results support contentions that ashwagandha supplementation (225 mg) may improve some measures of memory, attention, vigilance, attention, and executive function while decreasing perceptions of tension and fatigue in younger healthy individuals. Retrospectively registered clinical trial ISRCTN58680760.

Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run.

RATIONALE: Intense exercise promotes fatigue and can impair cognitive function, particularly toward the end of competition when decision-making is often critical for success. For this reason, athletes often ingest caffeinated energy drinks prior to or during exercise to help them maintain focus, reaction time, and cognitive function during competition. However, caffeine habituation and genetic sensitivity to caffeine (CA) limit efficacy. Paraxanthine (PX) is a metabolite of caffeine reported to possess nootropic properties. This study examined whether ingestion of PX with and without CA affects pre- or post-exercise cognitive function. METHODS: 12 trained runners were randomly assigned to consume in a double-blind, randomized, and crossover manner 400 mg of a placebo (PL); 200 mg of PL + 200 mg of CA; 200 mg of PL + 200 mg of PX (ENFINITY®, Ingenious Ingredients); or 200 mg PX + 200 mg of CA (PX+CA) with a 7-14-day washout between treatments. Participants donated fasting blood samples and completed pre-supplementation (PRE) side effects questionnaires, the Berg-Wisconsin Card Sorting Test (BCST), and the Psychomotor Vigilance Task Test (PVTT). Participants then ingested the assigned treatment and rested for 60 minutes, repeated tests (PRE-EX), performed a 10-km run on a treadmill at a competition pace, and then repeated tests (POST-EX). Data were analyzed using General Linear Model (GLM) univariate analyses with repeated measures and percent changes from baseline with 95% confidence intervals. RESULTS: BCST correct responses in the PX treatment increased from PRE-EX to POST-EX (6.8% [1.5, 12.1], p = 0.012). The error rate in the PL (23.5 [-2.8, 49.8] %, p = 0.078) and CA treatment (31.5 [5.2, 57.8] %, p = 0.02) increased from PRE-EX values with POST-EX errors tending to be lower with PX treatment compared to CA (-35.7 [-72.9, 1.4] %, p = 0.059). POST-EX perseverative errors with PAR rules were significantly lower with PX treatment than with CA (-26.9 [-50.5, -3.4] %, p = 0.026). Vigilance analysis revealed a significant interaction effect in Trial #2 mean reaction time values (p = 0.049, ηp2 = 0.134, moderate to large effect) with POST-EX reaction times tending to be faster with PX and CA treatment. POST-EX mean reaction time of all trials with PX treatment was significantly faster than PL (-23.2 [-43.4, -2.4] %, p = 0.029) and PX+CA (-29.6 [-50.3, -8.80] %, p = 0.006) treatments. There was no evidence that PX ingestion adversely affected ratings of side effects associated with stimulant intake or clinical blood markers. CONCLUSIONS: Results provide some evidence that pre-exercise PX ingestion improves prefrontal cortex function, attenuates attentional decline, mitigates cognitive fatigue, and improves reaction time and vigilance. Adding CA to PX did not provide additional benefits. Therefore, PX ingestion may serve as a nootropic alternative to CA.

Exploring the neuropharmacological potential of empagliflozin on nootropic and scopolamine-induced amnesic model of Alzheimer's like conditions in rats.

BACKGROUND: Alzheimer's disease (AD) is one of the most challenging and prevalent neurodegenerative disorder globally with a rising prevalence, characterized by progressive cognitive decline, memory loss, and behavioural changes. Current research aims to determine the nootropic and anti-amnesic effect of Empagliflozin (EMPA) against scopolamine-induced amnesia in rats, by modulating the cholinergic and N-Methyl D-Aspartate (NMDA) receptors. METHODS: Rats were treated once daily with an EMPA (5 and 10 mg/kg) and donepezil (2.5 mg/kg) for successive 26 days. During the final 13 days of treatment, a daily injection of scopolamine (1 mg/kg) was administered to induce cognitive deficits. RESULTS: EMPA was found to be significantly reduce escape latency, increase time spent in the target quadrant, and enhanced the number of target zone crossings in the Morris water maze (MWM) test, indicating improved spatial memory. Moreover, EMPA increased the recognition index and the number of spontaneous alternations in the novel object recognition (NOR) and Y-maze tests, respectively, suggesting enhanced memory. DISCUSSION: Interestingly doses of EMPA (5 mg/kg, 10 mg/kg) exhibited memory-enhancing effects even in the absence of scopolamine-induced impairment. Biochemical analysis revealed that EMPA elevated the levels of glutathione (GSH), a potent antioxidant, while decreasing lipid peroxidation (LPO) activity and increasing catalase (CAT) levels, indicating its antioxidative properties. Interestingly molecular docking studies revealed that EMPA fit perfectly in the active sites of M1 muscarinic acetylcholine (mACh) and NMDA receptors. These results indicated that the nootropic and antiamnesic effect of EMPA is possibly mediated via M1 and NMDA receptors and might be a remedy for AD.

[Cognitive impairment and tactics of using the drug Cerebrolysin. Resolution of the International Council of Experts (May 12, 2023)]. / Kognitivnye narusheniya i taktika primeneniya preparata Tserebrolizin. Rezolyutsiya mezhdunarodnogo soveta ekspertov (12 maya 2023 g.).

The aging of the population and the associated increase in the share of cognitive impairments in the structure of a wide range of diseases are a serious challenge for modern healthcare. Difficulties in the treatment of cognitive disorders are determined by many factors, including the age of patients, comorbidity, forced polypragmasia and the adequacy of the dosage of drugs that restore cognitive activity. The experts discussed information about the therapeutic potential of the drug Cerebrolysin in the treatment of cognitive disorders of various origins, stated significant experience of its effective and safe use in many clinical studies in mild and moderate forms of dementia. At the same time, there was a lack of consistent and systematic data on the dosage regimen, frequency, and duration of use of the drug in different forms of cognitive impairment and the degree of their severity. The aim of the international council of experts was to determine the optimal dosage regimens of the drug Cerebrolysin in patients with various etiologies and severity of cognitive impairment. The result of the work was the approval of a unified scheme for the use of the drug Cerebrolysin, considering the severity of the disease and its duration.

Personalized Response of Parkinson's Disease Gut Microbiota to Nootropic Medicinal Herbs In Vitro: A Proof of Concept.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons. Although the etiology of PD remains elusive, it has been hypothesized that initial dysregulation may occur in the gastrointestinal tract and may be accompanied by gut barrier defects. A strong clinical interest in developing therapeutics exists, including for the treatment of gut microbiota and physiology. We previously reported the impact of healthy fecal microbiota anaerobic cultures supplemented with nootropic herbs. Here, we evaluated the effect of nootropic Ayurvedic herbs on fecal microbiota derived from subjects with PD in vitro using 16S rRNA sequencing. The microbiota underwent substantial change in response to each treatment, comparable in magnitude to that observed from healthy subjects. However, the fecal samples derived from each participant displayed unique changes, consistent with a personalized response. We used genome-wide metabolic reconstruction to predict the community's metabolic potential to produce products relevant to PD pathology, including SCFAs, vitamins and amino acid degradation products. These results suggest the potential value of conducting in vitro cultivation and analyses of PD stool samples as a means of prescreening patients to select the medicinal herbs for which that individual is most likely to respond and derive benefit.

Nutrient Therapy for the Improvement of Fatigue Symptoms.

Fatigue, characterised by lack of energy, mental exhaustion and poor muscle endurance which do not recover following a period of rest, is a common characteristic symptom of several conditions and negatively impacts the quality of life of those affected. Fatigue is often a symptom of concern for people suffering from conditions such as fibromyalgia, chronic fatigue syndrome, cancer, and multiple sclerosis. Vitamins and minerals, playing essential roles in a variety of basic metabolic pathways that support fundamental cellular functions, may be important in mitigating physical and mental fatigue. Several studies have examined the potential benefits of nutrients on fatigue in various populations. The current review aimed to gather the existing literature exploring different nutrients' effects on fatigue. From the searches of the literature conducted in PubMed, Ovid, Web of Science, and Google scholar, 60 articles met the inclusion criteria and were included in the review. Among the included studies, 50 showed significant beneficial effects (p < 0.05) of vitamin and mineral supplementation on fatigue. Altogether, the included studies investigated oral or parenteral administration of nutrients including Coenzyme Q10, L-carnitine, zinc, methionine, nicotinamide adenine dinucleotide (NAD), and vitamins C, D and B. In conclusion, the results of the literature review suggest that these nutrients have potentially significant benefits in reducing fatigue in healthy individuals as well as those with chronic illness, both when taken orally and parenterally. Further studies should explore these novel therapies, both as adjunctive treatments and as sole interventions.

Post-Prandial Cognitive and Blood Pressure Effects of a DHA-Rich Omega-3 Powder in Middle-Aged Males: A Pilot Study.

The use of omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements is increasingly common among middle-aged and older adults. Users of ω-3 PUFA supplements often report using such supplements to support cognitive health, despite mixed findings reported within the ω-3 PUFA literature. To date, very few studies have explored cognitive effects in distinctly middle-aged (40 to 60 years) adults, and none have examined the acute effects (in the hours following a single dose) on cognitive performance. The current study evaluated whether a single dose of ω-3 PUFA (4020 mg docosahexaenoic acid and 720 mg eicosapentaenoic acid) influences cognitive performance and cardiovascular function in middle-aged males. Cognitive performance and cardiovascular function were assessed before and 3.5-4 h after consumption of a high dose of ω-3 PUFA (DHA + EPA) or placebo, incorporated into a standardized meal (i.e., single serve of Greek yogurt). In this study of middle-aged males, no significant differential treatment effects were observed for cognitive performance. However, a significant reduction in aortic systolic blood pressure (pre-dose to post-dose) was apparent following consumption of the ω-3 PUFA (DHA + EPA) treatment (mean difference = -4.11 mmHg, p = 0.004) but not placebo (mean difference = -1.39 mmHg, p = 0.122). Future replication in a sample comprising females, as well as patients with hypertension, is merited.

Vinpocetine protects against chloroquine-induced cardiotoxicity by mitigating oxidative stress.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are classical antimalarial drugs, and recently have been used for other applications including coronavirus disease 2019 (COVID-19). Although they are considered safe, cardiomyopathy may associate CQ and HCQ applications particularly at overdoses. The goal of the present study was to evaluate the potential protective effect of the nootropic agent vinpocetine against CQ and HCQ adverse effects with a specific focus on the heart. For this purpose, a mouse model of CQ (0.5 up to 2.5 g/kg)/HCQ (1 up to 2 g/kg) toxicity was used, and the effect of vinpocetine was evaluated by survival, biochemical, as well as histopathological analyses. Survival analysis revealed that CQ and HCQ caused dose-dependent lethality, which was prevented by co-treatment with vinpocetine (100 mg/kg, oral or intraperitoneal). To gain deeper understanding, a dose of 1 g/kg CQ-which did not cause death within the first 24 h after administration-was applied with and without vinpocetine administration (100 mg/kg, intraperitoneal). The CQ vehicle group showed marked cardiotoxicity as evidenced by significant alterations of blood biomarkers including troponione-1, creatine phosphokinase (CPK), creatine kinase-myocardial band (CK-MB), ferritin, and potassium levels. This was confirmed at the tissue level by massive alteration of the heart tissue morphology and coincided with massive oxidative stress. Interestingly, co-administration of vinpocetine strongly ameliorated CQ-induced alterations and restored the antioxidant-defense system of the heart. These data suggest that vinpocetine could be used as an adjuvant therapy together with CQ/HCQ applications.

Simultaneous determination of 11 nootropic substances potentially adulterated in dietary supplements for improving brain function using ultra-performance liquid chromatography and liquid chromatography-quadrupole-time-of-flight mass spectrometry.

Recently, the demand for improved brain function and concentration has increased in the dietary supplement market. However, to artificially enhance their pharmacological efficacy, dietary supplements may be illegally adulterated with unauthorised substances. Therefore, we developed a rapid and accurate method to simultaneously determine 11 nootropic substances using an ultra-high-performance liquid chromatography (UPLC) system equipped with a photodiode array (PDA) detector. In addition, sample preparation procedures were semi-optimised for various types of matrices, including solid (hard capsule, tablet, powder, and pill) and liquid (oil and extract) samples. The method was validated to determine the limit of detection (LOD), limit of quantification (LOQ), method detection limit (MDL), method quantitation limit (MQL), specificity, linearity, precision, accuracy, recovery, stability, and matrix effects. The validation results satisfied international validation guideline requirements. To test the applicability of the method, 55 real samples advertised as effective brain health, memory, and cognition supplements were analysed. Among the real samples, vinpocetine (2.483 and 7.296 µg/g), and kavain (69-44.056 µg/g) were detected. In addition, the detected compounds were confirmed by comparing their fragmentation patterns with those of the reference standards using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF/MS). In conclusion, the UPLC-PDA method not only rapidly and accurately quantifies illegal nootropics but also enables the pre-emptive investigation and identification of 11 nootropic substances in illegal dietary supplements to protect public health.

Effects of Dietary Supplementation of a Microalgae Extract Containing Fucoxanthin Combined with Guarana on Cognitive Function and Gaming Performance.

BACKGROUND: Esports competitive gaming requires selective visual attention, memory, quick judgment, and an ability to sustain psychomotor performance over time. Fucoxanthin is a carotenoid, found in specific microalgae varieties such as Phaeodactylum tricornutum (PT), that has been purported to possess nootropic and neuroprotective effects through its anti-inflammatory and antioxidant properties. This study evaluated whether acute and 30-day supplementation of an extract of PT from microalgae combined with guarana (a natural source of caffeine) affects cognitive function in gamers. MATERIALS AND METHODS: In a double-blind, placebo-controlled manner, 61 experienced gamers (21.7 ± 4.1 years, 73 ± 13 kg) were randomly assigned to ingest a placebo (PL), a low-dose (LD) supplement containing 440 mg of PT extract including 1% fucoxanthin +500 mg of guarana containing 40-44 mg caffeine (MicroPhyt™, Microphyt, Baillargues, FR), or a high-dose (HD) supplement containing 880 mg of PT extract +500 mg of guarana for 30 days. At baseline, cognitive function tests were administered before supplementation, 15 min post-supplementation, and after 60 min of competitive gameplay with participants' most played video game. Participants continued supplementation for 30 days and then repeated pre-supplementation and post-gaming cognitive function tests. General linear model univariate analyses with repeated measures and changes from baseline with 95% confidence intervals were used to analyze data. RESULTS: There was some evidence that acute and 30-day ingestion of the PT extract from microalgae with guarana improved reaction times, reasoning, learning, executive control, attention shifting (cognitive flexibility), and impulsiveness. While some effects were seen after acute ingestion, the greatest impact appeared after 30 days of supplementation, with some benefits seen in the LD and HD groups. Moreover, there was evidence that both doses of the PT extract from microalgae with guarana may support mood state after acute and 30-day supplementation. Registered clinical trial #NCT04851899.

Nootropic Activity of Prospekta in a Blind Placebo-Controlled Study in a Model of Focal Cerebral Ischemia in Rats.

Analysis of the pharmacological activity of the original drug Prospekta in a rat model of focal cerebral ischemia revealed its nootropic effect: course treatment in the post-ischemic period led to recovery of the neurological status of animals at the peak of neurological deficit. Evaluation of the therapeutic potential of the drug in morphological and functional CNS disorders allowed us to conclude that it is advisable to carry out further studies of its biological activity at the preclinical stage (the results obtained in animals were successfully confirmed in a clinical trial of drug efficacy in the treatment of moderate cognitive disorders in the early recovery period after ischemic stroke). Studies of the nootropic activity in other pathologies of the nervous system are also promising.

Influence of Murraya koenigii extract on diabetes induced rat brain aging.

Food supplements are used to improve cognitive functions in age-related dementia. This study was designed to determine the Murraya koenigii leaves' effect on Alloxan-induced cognitive impairment in diabetic rats and the contents of oxidative stress biomarkers, catalase, reduced glutathione, and glutathione reductase in brain tissue homogenates. Wistar rats were divided into seven groups (six rats per group). Group I received saline water (1 ml, p.o.), Diabetes was induced in Groups II-VII with Alloxan (120 mg/kg/p.o). Group III was provided with Donepezil HCl (2.5 mg/kg/p.o.), Group IV, V, VI, and VII with Murraya koenigii ethanol extract (200 and 400 mg/kg/p.o.) and aqueous extract (200 and 400 mg/kg/p.o.), respectively, for 30 days. Behavior, acetylcholinesterase (AChE) activity, oxidative stress status, and histopathological features were determined in the hippocampus and cerebral cortex. Administration of Murraya koenigii ethanolic and aqueous extracts significantly (P<0.05, P<0.001) increased the number of holes crossed by rats from one chamber to another. There was an increase in the (1) latency to reach the solid platform, (2) number of squares traveled by rats on the 30th day, and (3) percentage of spontaneous alternation behavior compared to the control group. Administration for successive days markedly decreased AChE activity (P<0.05), decreased TBARS level, and increased catalase, GSH, and GR levels. Murayya koenigii could be a promising food supplement for people with dementia. However, more research into sub-chronic toxicity and pharmacokinetic and pharmacodynamics interactions is essential.

Micropropagation and elicited production of triterpenoid saponin glycosides and stigmasterol via precursor and elicitor feeding in Bacopa floribunda (R.Br.) Wettst.-A potential nootropic herb.

Bacopa floribunda (Family: Plantaginaceae) is used in folklore medicines for the management of cognitive dysfunction. It has nootropic, antiaging, anti-inflammatory, anti-cholinesterase, and antioxidant properties. We developed an efficient and reproducible protocol for in vitro propagation of B. floribunda using the nodal explants. We assessed the effects of Murashige and Skoog (MS) medium fortified with various plant growth regulatory substances (PGRs), a precursor, and elicitors and their optimal combinations on regeneration and production of total saponins, triterpenoid saponin glycosides (bacoside A3, bacopaside X, bacopaside II, and bacosaponin C), and stigmasterol content in in vitro grown biomass of B. floribunda. The growth of the shoots and roots was stimulated by MS + 2.0 mg/l BAP + 2.0 mg/l KIN and MS + 0.5 mg/l IAA + 0.5 mg/l IBA + 1.0 mg/l NAA, respectively. After 10 weeks of acclimatization, plantlets of B. floribunda had a survival rate of 95%. The highest total saponin content (35.95 ± 0.022 mg DE/g DW) was noted in the treatment of MS + 2.0 mg/l BAP + 1.5 µM SQ. Similarly, total triterpenoid saponin glycosides and stigmasterol were found maximum in biomass derived from MS + 2.0 mg/l BAP + 1.5 µM SQ and MS + 2.0 mg/l BAP, respectively. At the same treatments, bacoside A3 (1.01 ± 0.195 mg/g DW), bacopaside II (43.62 ± 0.657 mg/g DW), bacopaside X (1.23 ± 0.570 mg/g DW), bacosaponin C (0.19 ± 0.195 mg/g DW), and stigmasterol (7.69 ± 0.102 mg/g DW) were reported. The present findings will help to highlight B. floribunda as a potent memory-enhancing herb, and in future also, it could be a potential substitute to B. monnieri. The current work is the first to describe the micropropagation and the elicited production of bioactive metabolites from the in vitro grown biomass of B. floribunda. In addition, further research is needed on production of bioactives, their pharmacological effects, and the elicited production using callus, cell suspension, and hairy root cultures.

Picamilon, a γ-aminobutyric acid (GABA) analogue and marketed nootropic, is inactive against 50 biological targets.

Picamilon is an analogue of the neurotransmitter γ-aminobutyric acid (GABA), which is marketed as a nootropic claiming to enhance cognition. There is a lack of in silico, in vitro and in vivo data on the safety of picamilon. Therefore, to ascertain potential physiological effects of picamilon, it was screened against 50 safety-related biological targets (receptors, ion channels, enzymes and transporters) by in silico and in vitro methods. Using two in silico tools, picamilon was not predicted to bind to the targets. Similarly, picamilon exhibited weak or no binding to the targets when measured in vitro at 10 µM. Overall, this data shows that picamilon, although structurally similar to other GABA analogues, has a different biological target binding profile. Picamilon's lack of binding to the 50 targets fills important data gaps among GABA analogues, a group of structurally related substances found in drugs and other consumer products.

Pyrimidine thioethers: A novel class of antidepressant agents, endowed with anxiolytic, performance enhancing and nootropic activity.

A series of new pyrimidine thioethers, recognized as the key intermediates in the synthesis of S-DABO antivirals, were prepared and evaluated both in vivo and in silico. The purpose of this evaluation was to find novel structural analogues of the known antihypoxic drug Isothiobarbamine endowed with improved pharmacological profile. The in vivo studies led to the identification of compounds 5c, 5e, and 5f endowed with antidepressant/anxiolytic, performance enhancing, and nootropic properties. Compounds 5c and 5f were further tested in mice affected by social depression and were able to increase motor and tentative search activity compared to control groups, along with higher interaction frequency and better results in a sucrose preference test. Overall, these data suggested a better psychoemotional state of the animals, treated with compounds 5c, and 5f. Moreover, 5c and 5f exhibited minimal acute toxicity, lower than Fluoxetine hydrochloride. Molecular modelling studies finally indicated the plausible biomolecular mechanism of action of compounds 5c, 5e, and 5f, which seem to bind GABA-A, melatonin, and sigma-1 receptors. Moreover, three-dimensional structure-activity relationships enabled to define a SAR model that will be of great utility for the design of further structurally optimized compounds of the above mentioned chemotype.

Current Trends in the Animal Models for Screening of Nootropic Agents: A Systematic Review.

BACKGROUND: Deficits in cognitive functions are observed in various diseases. The term "nootropics" refers to the compounds that increase mental functions, including memory, motivation, concentration and attention. Given the complexity and vastness of the processes involved in cognition, developing an appropriate animal model for the screening of nootropic agents still remains a daunting task. OBJECTIVES: This review attempts to elicit the current trends in the animal models being used for screening of nootropic agents and effectively use this knowledge to improve prospects embarking on this area of research. METHODS: Electronic searches were carried out on PubMed using the keywords "nootropic agents"[MeSH Term] OR "nootropic drugs" [MeSH Term] AND "animal model" [MeSH Term] OR "animal model, experimental" [MeSH Term]. All relevant studies from 2016 to 31st August, 2021, were then reviewed to meet the stated objective. RESULTS: The most commonly used disease model for screening of nootropic agents was found to be the animal model of Alzheimer's disease. Disease models of vascular dementia or stroke, depression or anxiety, schizophrenia, epilepsy or seizure, diabetes and traumatic brain injury, among others, have also been used. There exists a wide variety of behavioral tests to assess cognition. CONCLUSION: Since a variety of etiologies can affect cognitive processes. Hence, a nootropic agent may be screened in a variety of disease models. The most widely used and appropriate method to assess cognition would be by combining the behavioral and biochemical assays so that a more comprehensive profile of the nootropic effects of a drug can be elicited.

Phytochemistry and pharmacology of Celastrus paniculatus Wild.: a nootropic drug.

OBJECTIVES: Celastrus paniculatus Wild is an evergreen climbing shrub. The plant is of great significance in the traditional Indian System of Medicine, such as Ayurveda, Unani, and Siddha. The seeds and their oil are extensively used to treat neurological disorders such as cognitive dysfunction, paralysis, epilepsy, insomnia, and other ailments like rheumatism, arthritis, sciatica, and leprosy. This paper aims to highlight the nootropic activity of C. paniculatus and explore its phytochemistry, traditional uses, and other pharmacological activities. METHODS: All available information concerning C. paniculatus has been searched in the internationally accepted scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. Additional knowledge was gathered from the classical Textbooks and Unani Pharmacopoeia. RESULTS: C. paniculatus is a rich source of several secondary metabolites, such as ß-Dihydroagarofuranoids sesquiterpenes, alkaloids (Celastrine, Celapanin, Celapagin, and paniculatin), flavonoids, terpenoid (ß-amyrin, Lupeol, Pristimerin), sterols (ß-sitosterol, campesterol, stigmasterol, α-tocopherol, γ-Tocopherol), fatty acid (palmitic, stearic, oleic, linoleic, linolenic acids) and non-fatty acids (Benzoic acid, Cinnamic acid). The various study shows that the extracts and active constituent of this plant possess potent nootropic activity. Besides nootropic activity, it has also been reported for anti-Alzheimer, anticonvulsant, antidepressant, antioxidant, analgesic, anti-inflammatory, antiarthritic, gastroprotective, anti-psoriatic, wound healing, antibacterial, antimalarial, and several other properties. CONCLUSIONS: Several in vitro and in vivo trials confirm the conventional use of C. paniculatus in cognitive dysfunction. However, the relations between the possible mechanisms of other activities and traditional uses of the C. paniculatus remain indistinct. Still, pharmacological studies also explored the effects of C. paniculatus, which were not recognized in ancient times, such as cytotoxic, ACE inhibitor, and antidiabetic activities. These discoveries are may be beneficial in the development of the new drug to treat various diseases. It is also confirmed that the ß-dihydroagarofuranoids exhibit significant AChE inhibitory, cytotoxic, antibacterial, and insecticidal effects. This versatile medicine is truly a life elixir. Considering the therapeutic importance of the C. paniculatus and the absence of any reported clinical studies, extensive clinical trials are needed to explore its memory enhancing and other activities.

Nootropic activity of methanolic extract from Evolvulus alsinoides Linn. in mice with scopolamine-induced amnesia.

Plants have been used as therapeutic agents in both un-ionized (Unani, Ayurveda) and unstructured forms since ancient times. Therefore, it is of interest to document the nootropic activity of methanolic extract from Evolvulus alsinoides Linn (Vishnukranthi) in mice with scopolamine-induced amnesia. Healthy male Swiss albino mice ranging between 25 and 30 g were used in the study. Scopolamine induced amnesia, the following two tests are performed, elevated plus maze test, passive avoidance test. The mean time spent in the open arm, closed arm, and central platform for each group of animals. The total transitions were 12.6±0.89 by GS group mice, 3.4±0.55 by GSP group mice, 7±0.71 by GSLD group mice and 10±0.71 by GSHD group mice. A significant difference was seen between GS and GSP group mice means. The mean time in the safe zone and shock zone for each group of animals when comparing to Group 2 Vs Group 3, 4 showed a statistical significance of p < 0.05. The findings of this study suggest that Evolvulus alsinoides may be a promising candidate for the development of new treatments for memory impairment and other cognitive disorders. It should be noted that more data is needed to confirm the safety and efficacy of Evolvulus alsinoides in humans and to investigate its long-term effects.