Memory-enhancing Effects Research Articles

Alpinia officinarum Hance: a comprehensive review of traditional uses, phytochemistry, pharmacokinetic and pharmacology.

The dried root and rhizome of Alpinia officinarum Hance (A. officinarum) have been widely used in traditional Chinese medicine for thousands of years to alleviate pain, promote digestion, warm the stomach, and disperse cold. This review aims to comprehensively and in-depth summarize the most recent research on the traditional uses, phytochemistry, pharmacokinetics, and pharmacology of A. officinarum. By searching various databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, and China National Knowledge Infrastructure (CNKI) for literature on "A. officinarum Hance," as well as relevant textbooks and digital documents, an overall and critical review of the subject was conducted. The traditional uses of A. officinarum were summarized, and 337 compounds from A. officinarum were summarized, including flavonoids, diarylheptanoids, volatile oils, and other compounds. Studies have found that the crude extract of A. officinarum and its compounds has a wide range of biological activities, such as improving gastrointestinal function, anti-inflammatory properties, anti-tumor activity, antibacterial properties, memory enhancement, and analgesic effects. Modern pharmacological studies have provided strong evidence and explanations for the traditional medicinal uses of A. officinarum, which brings a broad prospect for its medicinal use. However, more research is needed to explore the structure-activity relationship and potential mechanisms of action of its bioactive chemicals. Furthermore, it is essential to conduct more clinical trials in order to accelerate research and development of the drug.

DHEA down-regulates mitochondrial dynamics and promotes apoptosis of lung adenocarcinoma cells through FASTKD2.

Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.

Long-term intermittent theta burst stimulation enhanced hippocampus-dependent memory by regulating hippocampal theta oscillation and neurotransmitter levels in healthy rats

Intermittent theta burst stimulation (iTBS), an updated pattern of high-frequency repetitive transcranial magnetic stimulation, is a potential candidate for improving memory. The hippocampus has been shown to be involved in the memory-enhancing effect induced by iTBS. However, it remains largely unknown whether this effect is achieved by regulating hippocampal theta oscillation and neurotransmitters gamma-aminobutyric acid (GABA) and glutamate, which are strongly related to memory. Thus, we investigated the effect of 14 days of iTBS on hippocampus-dependent memory and further explored the roles of hippocampal theta oscillation and neurotransmitters GABA and glutamate in this effect. We found that compared to sham iTBS, real iTBS enhanced hippocampus-dependent memory measured by hole-board test and object place recognition test. Further, real iTBS increased the density of c-Fos positive neurons and normalized power of theta oscillation in the dorsal hippocampus (dHip) compared to sham iTBS. Interestingly, we observed a decrease in the level of extracellular GABA and an increase in the level of extracellular glutamate in the dHip after real iTBS. Our results suggest that long-term iTBS improved hippocampus-dependent memory, which may be attributed to the enhancement of theta oscillation and altered levels of extracellular GABA and glutamate in the dHip.

Phyto-pharmacological Investigation of Plumbago zeylanica for Memory Enhancing Activity

Objective: The main goal was to assess the possible memory-enhancing effects of Plumbago zeylanica root extract on Wistar rats. Materials and Methods: Extract of P. zeylanica roots evaluated for memory enhancement by Morris water maze (MWM) and elevated plus maze (EPM). Here, the parameter examined was transfer latency (TL). Results: There was a dose-dependent decline in TL when P. zeylanica root extract was administered, as compared to the control. Conclusion: The observed dose-dependent reduction in transfer latency provides compelling evidence of the extract’s potential in countering neurodegeneration and affirming its nootropic capabilities.

Allosteric inhibition of phosphodiesterase 4D induces biphasic memory-enhancing effects associated with learning-activated signaling pathways.

Phosphodiesterase 4D negative allosteric modulators (PDE4D NAMs) enhance memory and cognitive function in animal models without emetic-like side effects. However, the relationship between increased cyclic adenosine monophosphate (cAMP) signaling and the effects of PDE4D NAM remains elusive. To investigate the roles of hippocampal cAMP metabolism and synaptic activation in the effects of D159687, a PDE4D NAM, under baseline and learning-stimulated conditions. At 3mg/kg, D159687 enhanced memory formation and consolidation in contextual fear conditioning; however, neither lower (0.3mg/kg) nor higher (30mg/kg) doses induced memory-enhancing effects. A biphasic (bell-shaped) dose-response effect was also observed in a scopolamine-induced model of amnesia in the Y-maze, whereas D159687 dose-dependently caused an emetic-like effect in the xylazine/ketamine anesthesia test. At 3mg/kg, D159687 increased cAMP levels in the hippocampal CA1 region after conditioning in the fear conditioning test, but not in the home-cage or conditioning cage (i.e., context only). By contrast, 30mg/kg of D159687 increased hippocampal cAMP levels under all conditions. Although both 3 and 30mg/kg of D159687 upregulated learning-induced Fos expression in the hippocampal CA1 30min after conditioning, 3mg/kg, but not 30mg/kg, of D159687 induced phosphorylation of synaptic plasticity-related proteins such as cAMP-responsive element-binding protein, synaptosomal-associated protein 25kDa, and the N-methyl-D-aspartate receptor subunit NR2A. Our findings suggest that learning-stimulated conditions can alter the effects of a PDE4D NAM on hippocampal cAMP levels and imply that a PDE4D NAM exerts biphasic memory-enhancing effects associated with synaptic plasticity-related signaling activation.

Reward conditioning may not have an effect on category-specific memory

Behavioural tagging facilitates the temporary storage of seemingly insignificant episodic events, which may later become salient and enhanced in memory. Human behavioural studies have demonstrated selective memory enhancement for neutral stimuli from one category when this category is subsequently paired with reward. Although this phenomenon has implications for the role of reward conditioning on emotional and adaptive memory, its generalisability is underexplored. We conducted four experiments to investigate whether pairing items from a semantic category, animals or objects, with high or low rewards resulted in preferential memory for the high-reward category. Three of these experiments also aimed to replicate the category-specific retrospective enhancement effect reported by Patil et al. and two explored the corresponding prospective memory effect. None of our experiments showed consistent evidence for an effect of reward on category-specific memory enhancement, despite employing the same reward paradigm and incidental encoding protocol as in the original study. Consequently, we found no evidence for category-specific retrospective or prospective enhancement effects. Our experiments were conducted online which is an equally relevant method for assessing behavioural phenomenon as the in-person studies conducted by Patil et al. Overall, our results question the generalisability of previously reported category-specific memory enhancement effects due to reward.

Tangeretin confers neuroprotection, cognitive and memory enhancement in global cerebral ischemia in rats.

Global cerebral ischemia is commonly associated with neurological deficits, including cognitive and memory impairments. The present study aims to investigate the neuroprotective, cognitive, and memory enhancement effects of Tangeretin, a flavonoid against global cerebral ischemia in rats. Bilateral common carotid artery occlusion (BCCAO) and reperfusion injury method was used to induce global cerebral ischemia in rats. Motor, cognitive, and memory functions were evaluated using rotarod, grip strength, Y-maze, and Morris water maze. Further, acetylcholine esterase (AchE) enzyme activity, acetylcholine (Ach), oxidative stress markers (ROS, SOD, MDA, and CAT), inflammation (IL-6 and TNF-α), and apoptotic markers (cytochrome C, caspase 9, and caspase 3) in BCCAO rats were measured following Tangeretin (5,10, and 20mg/kg, oral) treatment. Our findings show that Tangeretin treatment significantly improved cognition and memory by enhancing Ach levels through the amelioration of AchE enzyme activity in BCCAO rats. Moreover, Tangeretin exhibited neuroprotective effects through the mitigation of oxidative stress, inflammation, and apoptosis in the BCCAO rats. In summary, the current findings suggested that Tangeretin exhibited neuroprotection, cognitive and memory enhancement against global cerebral ischemia.

Evaluating the Mood and Memory-enhancing Effects of Punicagranatum Seeds (Pomegranate)Extract using an Animal Model

Evaluating the Mood and Memory-enhancing Effects of Punicagranatum Seeds (Pomegranate)Extract using an Animal Model

Natural Compounds of Salvia L. Genus and Molecular Mechanism of Their Biological Activity.

The study of medicinal plants is important, as they are the natural reserve of potent biologically active compounds. With wide use in traditional medicine and the inclusion of several species (as parts and as a whole plant) in pharmacopeia, species from the genus Salvia L. are known for the broad spectrum of their biological activities. Studies suggest that these plants possess antioxidant, anti-inflammatory, antinociceptive, anticancer, antimicrobial, antidiabetic, antiangiogenic, hepatoprotective, cognitive and memory-enhancing effects. Phenolic acids, terpenoids and flavonoids are important phytochemicals, which are primarily responsible for the medicinal activity of Salvia L. This review collects and summarizes currently available data on the pharmacological properties of sage, outlining its principal physiologically active components, and it explores the molecular mechanism of their biological activity. Particular attention was given to the species commonly found in Kazakhstan, especially to Salvia trautvetteri Regel, which is native to this country.

Increase in histone acetylation rescues a weak remote fear memory in rats

There is a growing body of evidence of memory-enhancing effects of histone deacetylase (HDAC) inhibitors in different species and models. Less clearly is understood whether the increased histone acetylation is able to facilitate the remote fear memory. Thus, the aim of the current study was to examine the ability of HDAC inhibitor sodium butyrate (SB) to ameliorate weakening of the remote fear memory in rats. To assess the ability of HDAC inhibitor SB to improve remote fear memory we compared the performance of two laboratory strains of rats, Wistar and Long-Evans, in context fear conditioning task six months after training before and after the SB administration. We found that the rats showed a strong fear response to the context 24 h after the end of conditioned fear training, full absence of fear after 6 months, and high fear response after the SB administration without additional learning. In control experiments, we found that time-dependent decrease in conditioned fear response to the context was similar in rats under vehicle administration. Moreover, the data obtained showed that both rats’ strains showed a similar decrease in freezing response over time, and HDAC inhibition improved the weak remote fear memory in both of them. In addition, the decrease in freezing and memory reinstatement by males matched completely to the female rats’ performance. These results indicate that HDAC inhibition appears to have the same “rescue” effects on remote fear memory reinstatement regardless of the strain and gender of rats.

A comparison of nutritional components and memory enhancement effects of HongJam prepared from different silkworm varieties that weave yellow-colored cocoons

Hongjam (HJ) is a natural health food made from mature silkworms, and various health-promoting effects of HJ have been reported. Recent studies have reported that the health-promoting effects of HJ vary depending on the color of the cocoon of the silkworm variety used for its production. Recently, we reported that Golden Silk (GS), a variety of silkworm with yellow cocoons, exhibit superior memory improvement effects when HJ derived from these silkworms is compared to other varieties. However, breeding lines used to produce silkworm varieties are maintained through inbreeding, which can lead to serious side effects in the case of the GS variety. Therefore, it is necessary to investigate the nutritional components and health-promoting effects of Daehwangjam (DHJ), a recently established yellow cocoon silkworm variety.A comparative study was conducted on the nutritional components and memory-enhancing effects of GS and DHJ-HJ. We found no significant differences in nutrient composition between GS- and DHJ-HJ as determined through proximate analysis, amino acid composition analysis, fatty acid content analysis and other methods. Additionally, in a rodent model of mild cognitive impairment, DHJ-HJ proved to be equally effective as GS-HJ. Since DHJ produces larger mature silkworms than GS, it will be possible to efficiently produce HJ for the purpose of creating memory enhancement health food.

Therapeutic Potential of Myrtenal and Its Derivatives-A Review.

The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a wide range in biological activities, including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, and vasodilating properties. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing effects in experimental dementia and Parkinson's disease. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive avenue within experimental pharmacology, offering a promising approach for the therapy of diverse pathological conditions. Biologically active substances such as monoterpenes, for example, borneol, camphor, geraniol, pinene, and thymol, are used to synthesize compounds with analgesic, anti-inflammatory, anticonvulsive, antidepressant, anti-Alzheimer's, antiparkinsonian, antiviral and antibacterial (antituberculosis) properties. Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, the conjugation of myrtenal with the established pharmacophore adamantane enables the augmentation of several of its pivotal properties. Myrtenal-adamantane derivatives exhibited a variety of beneficial characteristics, such as antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective properties, which are worth examining in more detail and at length.

RTI-263, a biased neuropeptide S receptor agonist that retains an anxiolytic effect, attenuates cocaine-seeking behavior in rats

Neuropeptide S (NPS) is a neuromodulatory peptide that acts via a G protein-coupled receptor. Centrally administered NPS suppresses anxiety-like behaviors in rodents while producing a paradoxical increase in arousal. In addition, NPS increases drug-seeking behavior when administered during cue-induced reinstatement. Conversely, an NPS receptor (NPSR) antagonist, RTI-118, decreases cocaine-seeking behavior. A biased NPSR ligand, RTI-263, produces anxiolytic-like effects and has memory-enhancing effects similar to those of NPS but without the increase in arousal. In the present study, we show that RTI-263 decreased cocaine seeking by both male and female rats during cue-induced reinstatement. However, RTI-263 did not modulate the animals’ behaviors during natural reward paradigms, such as palatable food intake, feeding during a fasting state, and cue-induced reinstatement of sucrose seeking. Therefore, NPSR biased agonists are a potential pharmacotherapy for substance use disorder because of the combined benefits of decreased drug seeking and the suppression of anxiety.

Neural representation of a one-week delay in remembering information after production and self-generated elaboration encoding strategy

Many studies have confirmed the memory enhancement effect of production, generation and elaboration which can be effective after only one encoding. It is also known that greater memory enhancement effects can be obtained by combining multiple memory strategies during encoding. This study aimed to investigate whether the combination of production and self-generated elaboration enhances memory performance compared with production or generation alone. A total of 23 undergraduate and graduate students participated in this study. In the functional magnetic resonance imaging analysis, we explored the neural representation of remembering information after production and self-generated elaboration strategy. We set four encoding strategy conditions: (1) Read Silent (read without production), (2) Read Aloud (only production), (3) Add Silent (self-generated elaboration without production), (4) Add Aloud (production and self-generated elaboration). The retrieval performance and brain activity while retrieving the learned sentences after a one-week delay were examined. The behavioral results showed that the highest memory performance was for sentences encoded in Add Aloud. The interaction between production and self-generated elaboration was statistically significant. These results suggest that the memory enhancement effect of combining production and self-generated elaboration is not a simple addition nor synergistic facilitation effect. The imaging results showed that the following areas were related to the retrieval of the target encoded in the add aloud condition: the area related to integration of internal and external information (precuneus), area related to information rich stimuli (lateral occipital lobe), area related to self-involvement and inference of others' feelings (MPFC), area related to seen imagery (retrosplenial region) and area related to adjustment of movement (cerebellum). These results suggest that with an encoding strategy that combines production and self-generated elaboration, integrated auditory input of vocalizations and generated images, visual images of the scene, self-relevance, inference of other's feeling, movement by moving mouth are stored with the target and enhanced memory performance of AA.

Mastication stimuli regulate the heartbeat rate through rhythmic regulation by the hypothalamic-autonomic system; molecular and telemetric studies in weaning-stage rats.

Mastication stimuli have been demonstrated to affect memory function and autonomic nerve activity; however, this process has not been well studied during weaning compared to old age. Previously, we conducted molecular analyses of the thalamus and hippocampus to elucidate the mechanisms underlying this memory-enhancing effect in weaning-stage rats. In this study, we aimed to evaluate the effect of masticatory stimuli on the regulation of heartbeat rate (HR) through the hypothalamic-autonomic system. Three-week-old male rats were administered a powdered diet (P group) or chow-diet (C group) for 10 days. Thereafter, transcriptome analysis was performed. Vasopressin, cocaine-amphetamine-regulated transcript prepropeptide, corticotropin-releasing hormone, and thyrotropin-releasing hormone, which are involved in sympathetic activation of heart rate, were downregulated in the C group. Electrocardiograms were recorded continuously for 12 days under the same condition. Interestingly, rats in the C group had a significantly lower HR than those in the P group on day 11. We checked several parameters representing the autonomic regulation of HR. The C group had higher values for the high-frequency band integration of the HR power spectrum (parasympathetic marker) and root mean square successive difference of R-wave intervals (parasympathetic marker) relative to the P group. Such findings provide a molecular and physiological basis for understanding the regulation of cardiovascular function in response to masticatory stimuli in the autonomic nervous system.

Anti-rheumatic and Memory-enhancing Effect of Memantine on Complete Freund’s Adjuvant-induced Rheumatoid Arthritis Compared to Methotrexate in Wistar Rats

Objectives To evaluate the anti-inflammatory and memory-enhancing effects of memantine (MEM) in complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) in Wistar rats. The effect of MEM on cognition in CFA-induced RA was also evaluated. Materials and Methods The rats were randomly assigned to one of five groups: sham control (SC), disease control (DC)—CFA 0.1 mg, positive control (PC)—methotrexate (MTX) 1 mg/kg, low dose MEM—20 mg/kg, and high dose MEM (HD-M)—50 mg/kg. All groups received a subcutaneous injection of CFA in the left paw on day 0, except for the SC group, which received a distilled water (DW) injection. The study drugs, MEM and MTX, were administered orally from days 15 to 28. The SC group received DW orally from days 15 to 28. Variables for physical (paw volume, paw surface temperature, and ankle joint diameter) and behavior (open field test, grip strength test, and water corn test) were performed on days 1, 0, 7, 14, 21, and 28. On day 28, blood was collected for serum inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Ex vivo radiological changes in the ankle joint were recorded using a digitalized X-ray machine. Histopathology of the ankle joint was performed. Results When compared to the DC group, the HD-M group showed a significant improvement in all physical and behavioral characteristics ( p < 0.001). When compared to the DC group, TNF-α, IL-6 levels, and histopathological scores were significantly lower in the HD-M group ( p < 0.01). Conclusion MEM reduces inflammation and improves memory in Wistar rats with CFA-induced RA. MEM can be used as an anti-inflammatory drug in elderly patients at risk of dementia.

Impact of levetiracetam on cognitive impairment, neuroinflammation, oxidative stress, and neuronal apoptosis caused by lipopolysaccharides in rats

IntroductionNeuroinflammation is associated with the elevation of toxic proinflammatory mediators that promote neurodegeneration and subsequently affect cognition. Causes of inflammation in the neuronal cells are believed to initiate various neurodegenerative disorders, mainly Alzheimer’s disease. Levetiracetam is a second-generation antiepileptic drug. There is evidence supporting the memory-enhancing effect of levetiracetam from numerous experimental and clinical studies. Therefore, this research focused on finding its protective effects against lipopolysaccharides prompted cognitive impairment and exploring possible mechanisms underlining their neuroprotection. MethodologyTwo doses (100 or 200 mg/kg) of levetiracetam were administrated orally for 30 days. Additionally, four doses (250 µg/kg) of lipopolysaccharide were injected peripherally to induce neurotoxicity. Behavioral tests were carried out using various maze models. At the end of the tests, brain tissues were collected for biochemical evaluations. Cholinergic, neuroinflammatory, apoptosis, and oxidative-related parameters were analyzed in the brain homogenate to explore the possible mechanisms of action of levetiracetam. ResultsIn lipopolysaccharide-induced rats, levetiracetam indicated a reduction (p < 0.01) in transfer latency using the elevated plus-maze. An improvement (p < 0.01) in novel and familiar objects exploration time using novel object recognition test. A rise (p < 0.05) in novel arm entries and extended time spent in the novel arm using the Y-maze test. In extension, the levels of acetylcholine (p < 0.001), anti-inflammatory factors (transforming growth factor-β1; p < 0.01 and interleukin-10; p < 0.05), and an antioxidant (catalase; p < 0.01) were elevated in lipopolysaccharide-induced rats after the administration of levetiracetam. In contrast, inflammatory factors (cyclooxygenase-2; p < 0.05, nuclear factor kappa B; p < 0.05, tumor necrosis factor-α; p < 0.01, and interleukin-6 (p < 0.01), apoptosis inducers (BCL2-associated X protein; p < 0.05 and Caspase-3 (p < 0.001), and oxidative stress (malondialdehyde; p < 0.05) were considerably reduced with levetiracetam in lipopolysaccharide-induced rats. ConclusionThe collective results suggested that levetiracetam may be able to treat neuroinflammatory-related memory loss by enhancing cholinergic activity while reducing neuroinflammation, cellular apoptosis, and oxidative stress.

Ranuncoside’s attenuation of scopolamine-induced memory impairment in mice via Nrf2 and NF-ĸB signaling

Scopolamine is a well-known pharmacological agent responsible for causingmemory impairmentin animals, as well as oxidative stress and neuroinflammation inducer which lead to the development of Alzheimer disease. Although a cure for Alzheimer’s disease is unavailable. Ranuncoside, a metabolite obtained from a medicinal plant has demonstrated antioxidant and anti-inflammatory properties in vitro, making it a promising treatment with potential anti-Alzheimer disease properties. However, as ranuncoside has not been evaluated for its antioxidant and anti-neuroinflammatory properties in any in vivo model, our study aimed to evaluate its neurotherapeutic efficacy against scopolamine-induced memory impairment in adult male albino mice.Mice were randomly divided into four experimental groups. Mice of group I was injected with saline, group II was injected with scopolamine (1 mg/kg/day) for 3 weeks. After receiving a daily injection of scopolamine for 1 week, the mice of group III were injected with ranuncoside (10 mg/kg) every other day for 2 weeks along with scopolamine daily and group IV were injected with ranuncoside on 5th alternate days. Behavioral tests (i.e., Morris water maze and Y-maze) were performed to determine the memory-enhancing effect of ranuncoside against scopolamine's memory deleterious effect. Western blot analysis was also performed to further elucidate the anti-neuroinflammatory and antioxidant effects of ranuncoside against scopolamine-induced neuroinflammation and oxidative stress.Our results showed memory-enhancing, anti-neuroinflammatory effect, and antioxidant effects of ranuncoside against scopolamine by increasing the expression of the endogenous antioxidant system (i.e., Nrf2 and HO-1), followed by blocking neuroinflammatory markers such as NF-κB, COX-2, and TNF-α. The results also revealed that ranuncoside possesses hypoglycemic and hypolipidemic effects against scopolamine-induced hyperglycemia and hyperlipidemia in mice as well as scopolamine’s hyperglycemic effect. In conclusion, our findings suggest that ranuncoside could be a potential agent for the management of Alzheimer’s disease, hyperglycemia, and hyperlipidemia.

Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence

BackgroundEthanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear. MethodsTwenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups. ResultsWhile the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters. ConclusionThe memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes.

Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases.

Animal survival depends on cognitive abilities such as learning and memory to adapt to environmental changes. Memory functions require an enhanced activity and connectivity of a particular arrangement of engram neurons, supported by the concerted action of neurons, glia, and vascular cells. The deterioration of the cholinergic system is a common occurrence in neurological conditions exacerbated by aging such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), Alzheimer's disease (AD), and Parkinson's disease (PD). Cotinine is a cholinergic modulator with neuroprotective, antidepressant, anti-inflammatory, antioxidant, and memory-enhancing effects. Current evidence suggests Cotinine's beneficial effects on cognition results from the positive modulation of the α7-nicotinic acetylcholine receptors (nAChRs) and the inhibition of the toll-like receptors (TLRs). The α7nAChR affects brain functions by modulating the function of neurons, glia, endothelial, immune, and dendritic cells and regulates inhibitory and excitatory neurotransmission throughout the GABA interneurons. In addition, Cotinine acting on the α7 nAChRs and TLR reduces neuroinflammation by inhibiting the release of pro-inflammatory cytokines by the immune cells. Also, α7nAChRs stimulate signaling pathways supporting structural, biochemical, electrochemical, and cellular changes in the Central nervous system during the cognitive processes, including Neurogenesis. Here, the mechanisms of memory formation as well as potential mechanisms of action of Cotinine on memory preservation in aging and neurological diseases are discussed.