Effect of grewia hirsuta vahl ethanolic root extract on cognition in scopolamine induced amnesia

Objective Alzheimer's illnesses are becoming medical nightmares because there is no exact solution and existing nootropic medicines (Piracetam, tacrine, and metrifonate) have significant drawbacks. The goal of this study was to see if the ethanolic root extract of Grewia hirsuta (ERGH) could improve memory in rats who had been given scopolamine. Materials and procedures At rats, ERGH was given orally in dosages of 200 and 400 mg/kg for 28 days, followed by Scopolamine (18 mg/kg i.p.) from the 25th to the 27th day. The usual nootropic drug was piracetam (200 mg/kg). The elevated plus maze (EPM), Morris water maze (MWM), and passive avoidance (PA) paradigms are used to assess cognitive functioning. Invivo anti-oxidant activity and brain acetylcholine esterase (AchE) activity were assessed. Results: At the indicated doses, ERGH extract showed a substantial memory-enhancing activity by decreasing the transfer latency in EPM, increasing the escape latency in MWM, and increasing the shock-free zone in PA. In scopolamine-induced amnesia rats, pretreatment with ERGH resulted in a significant drop in AchE enzyme, an increase in enzymatic antioxidant, and a decrease in MDA levels. Conclusion Because of its several favorable benefits, such as memory-improving properties, anticholinesterase activity, and antioxidant activity, ERGH may prove to be a useful drug in the current study, and it would be important to investigate its potential in the care of Alzheimer's patients.

Influence of psychostimulants and opioids on epigenetic modification of class III histone deacetylase (HDAC)-sirtuins in glial cells

Substance abuse affects the central nervous system (CNS) and remains a global health problem. Psychostimulants, such as cocaine and methamphetamine (METH), and opioids affect neuronal function and lead to behavioral impairments via epigenetic modification. Epigenetic changes occur via classical pathways, especially the class III histone deacetylase (HDAC)-sirtuin (SIRT) family, that act as cellular sensors to regulate energy homeostasis and coordinate cellular responses to maintain genome integrity. However, SIRT family (1–7)-associated neurodegeneration has not been elucidated in the context of energy metabolism. The present study examined the effects of psychostimulants, such as cocaine and METH, and opioids, such as morphine, on SIRT family (1–7) [class I, II, III and IV] expression and cellular translocation-mediated dysfunction in astrocytes and microglial cells. The “nootropic” drug piracetam played a preventative role against psychostimulant- and opioid-induced SIRT (1–7) expression in astrocytes. These results indicate that cocaine, METH, and morphine affected deacetylation and cellular function, and these changes were prevented by piracetam in astrocytes.

Pharmacological correction of antioxidant protection system in the brain with Vincamine within the model of multiple sclerosis

Objective. In the course of the research, the effect of vincamine (nootropic drug) on neurological status, as well as the activity of antioxidant enzymes and the level of their coding genes’ expression in the somatosensory cortex of rats within the model of experimental allergic encephalomyelitis (EAE) were being studied. Relevance: the topicality of studying the mechanisms of multiple sclerosis in the early stages of its development is dictated by the need to search for markers of the disease and its therapy before the onset of its clinical manifestation. Materials and methods. The animals’ neurological status was studied using muscular strength, balance, tenacity and traction tests. Rates of survival and the rats’ body weight were also being evaluated. The study of activity antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPO), and glutathione reductase (GR), as well as the expression of SOD1, GPX4, GPX6, and GSR genes was conducted on the 14th and 30th day of immunization. Results. The percentage of vincamine-injected animals’ survival was 100% versus 87% among rats that were not injected with the nootropic drug during immunization (р<0,05) . Besides, after the injection of vincamine, a less significant decrease in body weight (р<0,01) and a less pronounced neurological deficit (р<0,05) in comparison with immunized non-injected animals were reported. The vincamine injection contributed to an increase in all studied antioxidant enzymes’ activity and the level of their genes’ expression in the somatosensory cortex. Conclusion. Against the background of vincamine injection, a minimization of neurological deficit is being observed, probably due to a decrease in oxidative stress in the rat brain during the clinical stage of experimental allergic encephalomyellitis.

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 β-Dihydroagarofuranoids sesquiterpenes, alkaloids (Celastrine, Celapanin, Celapagin, and paniculatin), flavonoids, terpenoid (β-amyrin, Lupeol, Pristimerin), sterols (β-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 β-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.

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

Illicit drugs are known to affect central nervous system (CNS). Majorly psychostimulants such as cocaine, methamphetamine (METH) and opioids such as morphine are known to induce epigenetic changes of histone modifications and chromatin remodeling which are mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Aberrant changes in histone acetylation-deacetylation process further exacerbate dysregulation of gene expression and protein modification which has been linked with neuronal impairments including memory formation and synaptic plasticity. In CNS, astrocytes play a pivotal role in cellular homeostasis. However, the impact of psychostimulants and opioid mediated epigenetic changes of HAT/HADCs in astrocytes has not yet been fully elucidated. Therefore, we have investigated the effects of the psychostimulants and opioid on the acetylation-regulating enzymes- HAT and HDACs role in astrocytes. In this study, Class I and II HDACs and HATs gene expression, protein changes and global level changes of acetylation of H3 histones at specific lysines were analyzed. In addition, we have explored the neuroprotective “nootropic” drug piracetam were exposed with or without psychostimulants and opioid in the human primary astrocytes. Results revealed that psychostimulants and opioid upregulated HDAC1, HDAC4 and p300 expression, while HDAC5 and GCN5 expression were downregulated. These effects were reversed by piracetam coexposure. Psychostimulants and opioid exposure upregulated global acetylation levels of all H3Ks, except H3K14. These results suggest that psychostimulants and opioids differentially influence HATs and HDACs.

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.

How Does Caffeine Influence Memory? Drug, Experimental, and Demographic Factors

Caffeine is a widely used nootropic drug, but its effects on memory in healthy participants have not been sufficiently evaluated. Here we review evidence of the effects of caffeine on different types of memory, and the associated drug, experimental, and demographical factors. There is limited evidence that caffeine affects performance in memory tasks beyond improved reaction times. For drug factors, a dose-response relationship may exist but findings are inconsistent. Moreover, there is evidence that the source of caffeine can modulate its effects on memory. For experimental factors, past studies often lacked a baseline control for diet and sleep and none discussed the possible reversal of withdrawal effect due to pre-experimental fasting. For demographic factors, caffeine may interact with sex and age, and the direction of the effect may depend on the dose, individual tolerance, and metabolism at baseline. Future studies should incorporate these considerations, as well as providing continued evidence on the effect of caffeine in visuospatial, prospective, and implicit memory measures.

A Review on Synthesis and Pharmacological Activities of Piracetam and its Derivatives

Piracetam is generally utilized as a nootropic drug, which is normally used in the treatment of CNS disorders. Piracetam is a cyclic compound and a derivative of γ-aminobutyric acid and improves learning, memory, brain metabolism, and ability. This drug belongs to the racetams group with the chemical name 2-oxo-1-pyrrolidine acetamide. The emphasis of this review article is to highlight different biological activities associated with piracetam and also some of its synthetic methodologies. Promising effects have been achieved in the management and treatment of several diseases for example alcoholism, Raynaud’s phenomenon, deep vein thrombosis and brain injury.

Neuroprotective Effect of Piracetam against Cocaine-Induced Neuro Epigenetic Modification of DNA Methylation in Astrocytes

Cocaine abuse is known to alter mitochondrial biogenesis and induce epigenetic modification linked with neuronal dysfunction. Cocaine-induced epigenetic modification of DNA methylation and the mitochondrial genome may affect mitochondrial DNA (mtDNA) and nuclear DNA (nDNA), as epigenetic DNA methylation is key to maintaining genomic integrity in the central nervous system (CNS). However, the impact of cocaine-mediated epigenetic changes in astrocytes has not yet been elucidated. In this study, we explored the neuroprotective effect of piracetam against cocaine-induced epigenetic changes in DNA methylation in astrocytes. To study our hypothesis, we exposed human astrocytes to cocaine alone or in combination with the nootropic drug piracetam. We examined the expression of the DNA methyltransferases (DNMTs) DNMT-1, DNMT-3A, and DNMT-3B; global DNA methylation levels of 5-methycytosine (5-mC); and induction of ten–eleven translocation (TET) enzymes in astrocytes. In addition, we analyzed mtDNA methylation by targeted next-generation bisulfite sequencing. Our data provide evidence that cocaine impairs DNMT activity and thereby has impacts on mtDNA, which might contribute to the neurodegeneration observed in cocaine users. These effects might be at least partially prevented by piracetam, allowing neuronal function to be maintained.