Rosmarinus officinalis and Mentha piperita Oils Supplementation Enhances Memory in a Rat Model of Scopolamine-Induced Alzheimer's Disease-like Condition.

Alzheimer's disease is regarded as a common neurodegenerative disease that may lead to dementia and the loss of memory. We report here the nootropic and anti-amnesic effects of both peppermint and rosemary oils using a rat model of scopolamine-induced amnesia-like AD. Rats were administered orally with two doses (50 and 100 mg/kg) of each single oil and combined oils. The positive group used donepezil (1 mg/kg). In the therapeutic phase, rats were administered scopolamine (1 mg/kg) through the oral administration of oils. During the nootropic phase, both oils showed a significant (p < 0.05) decrease in radial arm maze latency times, working memory, and reference memory errors compared with the normal group, along with significant (p < 0.05) enhancements of long-term memory during the passive avoidance test. Therapeutic phase results revealed significant enhancements of memory processing compared with the positive groups. In the hippocampus, oils exhibited an elevation of BDNF levels in a dose-dependent manner. Immunohistochemistry findings showed increased hippocampal neurogenesis suppressed by scopolamine in the sub-granular zone, and the anti-amnesic activity of single oil was enhanced when the two oils combined. Gas chromatography-mass spectrometry (GCMS) of the two oils revealed sufficient compounds (1,8-Cineole, α-Pinene, menthol and menthone) with potential efficacy in the memory process and cognitive defects. Our work suggests that both oils could enhance the performance of working and spatial memory, and when combined, more anti-amnesic activity was produced. A potential enhancement of hippocampal growth and neural plasticity was apparent with possible therapeutic activity to boost memory in AD patients.

Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs.

Nootropics, also known as "smart drugs" are a diverse group of medicinal substances whose action improves human thinking, learning, and memory, especially in cases where these functions are impaired. This review provides an up-to-date overview of the potential effectiveness and importance of nootropics. Based on their nature and their effects, this heterogeneous group of drugs has been divided into four subgroups: classical nootropic compounds, substances increasing brain metabolism, cholinergic, and plants and their extracts with nootropic effects. Each subgroup of nootropics contains several main representatives, and for each one, its uses, indications, experimental treatments, dosage, and possible side effects and contraindications are discussed. For the nootropic plant extracts, there is also a brief description of each plant representative, its occurrence, history, and chemical composition of the medicinal part. Lastly, specific recommendations regarding the use of nootropics by both ill and healthy individuals are summarized.

The Efficacy and Safety of Alzheimer's Disease Therapies: An Updated Umbrella Review.

BACKGROUND: Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse. OBJECTIVE: We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients. METHODS: We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles. RESULTS: Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Aß agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD. CONCLUSION: Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD.

Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats.

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is unknown. We conducted a proteomic study on the hippocampal synaptosomal fractions of adult male Wistar rats exposed to chronic social isolation (CSIS, 6 weeks), an animal model of depression and after chronic Tian treatment in controls (nootropic effect) and CSIS-exposed rats (lasting 3 weeks of 6-week CSIS) (therapeutic effect). Increased expression of Syn1 and Camk2-related neurotransmission, vesicle transport and energy processes in Tian-treated controls were found. CSIS led to upregulation of proteins associated with actin cytoskeleton, signaling transduction and glucose metabolism. In CSIS rats, Tian up-regulated proteins involved in mitochondrial energy production, mitochondrial transport and dynamics, antioxidative defense and glutamate clearance, while attenuating the CSIS-increased glycolytic pathway and cytoskeleton organization proteins expression and decreased the expression of proteins involved in V-ATPase and vesicle endocytosis. Our overall findings revealed that synaptic vesicle dynamics, specifically exocytosis, and mitochondria-related energy processes might be key biological pathways modulated by the effective nootropic and antidepressant treatment with Tian and be a potential target for therapeutic efficacy of the stress-related mood disorders.

Experimental evidence and mechanism of action of some popular neuro-nutraceutical herbs.

Brain and neuronal circuits constitute the most complex organ networks in human body. They not only control and coordinate functions of all other organs, but also represent one of the most-affected systems with stress, lifestyle and age. With global increase in aging populations, these neuropathologies have emerged as major concern for maintaining quality of life. Recent era has witnessed a surge in nutritional remediation of brain dysfunctions primarily by "nutraceuticals" that refer to functional foods and supplements with pharmacological potential. Specific dietary patterns with a balanced intake of carbohydrates, fatty acids, vitamins and micronutrients have also been ascertained to promote brain health. Dietary herbs and their phytochemicals with wide range of biological and pharmacological activities and minimal adverse effects have gained remarkable attention as neuro-nutraceuticals. Neuro-nutraceutical potentials of herbs are often expressed as effects on cognitive response, circadian rhythm, neuromodulatory, antioxidant and anti-inflammatory activities that are mediated by effects on gene expression, epigenetics, protein synthesis along with their turnover and metabolic pathways. Epidemiological and experimental evidence have implicated enormous applications of herbal supplementation in neurodegenerative and psychiatric disorders. The present review highlights the identification, experimental evidence and applications of some herbs including Bacopa monniera, Withania somnifera, Curcuma longa, Helicteres angustifolia, Undaria pinnatifida, Haematococcus pluvialis, and Vitis vinifera, as neuro-nutraceuticals.

Enzyme-assisted Solvent Extraction of High-yield Paeonia suffruticosa Andr. Seed Oil and Fatty Acid Composition and Anti-Alzheimer's Disease Activity.

Enzyme-assisted solvent extraction (EASE) of Paeonia suffruticosa Andr. seed oil (PSO) was optimized by response surface methodology (RSM). The fatty acid composition and anti-Alzheimer's disease (AD) activity of PSO were analyzed. An enzyme mixture composed of cellulase and hemicellulase (1:1, w/w) was most effective in determining the extraction yield of PSO. The ideal extraction conditions were a pH value of 5.1, an enzymolysis time of 68 min, and a temperature of 50℃. The average extraction yield of PSO was 38.2 mL/100 g, 37.4% higher than that of untreated peony seed (27.8 mL/100 g). The fatty acid composition of PSO under optimal conditions for EASE was analyzed by gas chromatography-mass spectrometry (GC-MS). The predominant unsaturated fatty acids of PSO were determined to be more than 90.00%, including n-3 α-linolenic acid (43.33%), n-6 linoleic acid (23.40%) and oleic acid (23.59%). In this experiment, the anti-AD effect of PSO was also analyzed by performing learning and memory ability tests with Drosophila. PSO retarded the decrease in climbing ability in AD Drosophila. The 1% and 5% PSO groups were significantly different from the model group (b p < 0.05). The smell short-term memory ability test revealed the number of Drosophila in barrier and barrier-free centrifuge tubes in each group. PSO feeding improved learning and memory in AD Drosophila, with the highest number entering the barrierfree centrifuge tube. The performance index (PI) measured by the Pavlov olfactory avoidance conditioning test also demonstrated the effect of PSO on the learning and memory abilities of Drosophila. The PI of the PSO group was significantly increased compared to that of the model group. HE-stained brain tissue sections of AD Drosophila showed higher neurodegenerative changes, while PSO significantly reduced neurodegenerative damage. These results indicated that PSO can significantly improve the cognitive function of AD Drosophila and may help to prevent AD.

Activity of Selected Group of Monoterpenes in Alzheimer's Disease Symptoms in Experimental Model Studies-A Non-Systematic Review.

Alzheimer's disease (AD) is the leading cause of dementia and cognitive function impairment. The multi-faced character of AD requires new drug solutions based on substances that incorporate a wide range of activities. Antioxidants, AChE/BChE inhibitors, BACE1, or anti-amyloid platelet aggregation substances are most desirable because they improve cognition with minimal side effects. Plant secondary metabolites, used in traditional medicine and pharmacy, are promising. Among these are the monoterpenes-low-molecular compounds with anti-inflammatory, antioxidant, enzyme inhibitory, analgesic, sedative, as well as other biological properties. The presented review focuses on the pathophysiology of AD and a selected group of anti-neurodegenerative monoterpenes and monoterpenoids for which possible mechanisms of action have been explained. The main body of the article focuses on monoterpenes that have shown improved memory and learning, anxiolytic and sleep-regulating effects as determined by in vitro and in silico tests-followed by validation in in vivo models.

Ilex kudingcha C.J. Tseng Mitigates Phenotypic Characteristics of Human Autism Spectrum Disorders in a Drosophila Melanogaster Rugose Mutant.

Autism spectrum disorders (ASD) have heterogeneous etiologies involving dysfunction of central nervous systems, for which no effective pan-specific treatments are available. Ilex kudingcha (IK) C.J. Tseng is a nootropic botanical used in Asia for neuroprotection and improvement of cognition. This study establishes that a chemically characterized extract from IK (IKE) mitigates behavioral traits in the Drosophila melanogaster rugose mutant, whose traits resemble human ASD, and examines possible mechanisms. IKE treatment significantly ameliorated deficits in social interaction, short-term memory, and locomotor activity in Drosophila rugose, and significantly increased synaptic bouton number of size more than 2 µm2 in the neuromuscular junctions (NMJs) of Drosophila rugose. To clarify mechanism(s) of IKE action, methylphenidate (MPH), a dopamine transporter inhibitor, was included as a reference drug in the behavioral assays: MPH significantly improved social interaction and short-term memory deficit in Drosophila rugose; administration of the dopamine D1 receptor antagonist SCH23390 and dopamine D2 receptor antagonist sulpiride reversed the ameliorative effects of both MPH and IKE on the social interaction deficits of Drosophila rugose. To extend analysis of IKE treatment to the vertebrate central nervous system, ASD-associated gene expression in mouse hippocampus was studied by RNA-seq: IKE treatment altered the expression of genes coding phosphoinositide 3-kinases/protein kinase B (PI3K-Akt), proteins in glutamatergic, dopaminergic, serotonergic, and GABAergic synapses, cAMP response element-binding protein (CREB), and RNA transporter proteins. These results provide a foundation for further analysis of IKE as a candidate for treatment of some forms of ASD.

Preclinical systematic review of ginsenoside Rg1 for cognitive impairment in Alzheimer's disease.

Ginseng has been used for the treatment of aging and memory impairment for thousands of years. Several studies have found that ginsenoside Rg1, as one of the main active components of ginseng, could potentially improve cognitive function in several different animal models. A preclinical systematic review to evaluate the efficacy and mechanisms of ginsenoside Rg1 for ameliorating cognitive impairments in Alzheimer's disease is reported here. We searched six databases from their inceptions to January 2019. Thirty-two studies were selected, which included a total of 1,643 animals. According to various cognitive behavioral tests, the results of the meta-analyses showed that ginsenoside Rg1 significantly improved cognitive behavioral impairments in most Alzheimer's disease models (P < 0.05), but there were no significant effects in animals with neuronal degeneration induced by chronic stress or in SAMP8 transgenic mice. The potential mechanisms included antioxidant and anti-inflammatory effects, amelioration of Alzheimer's disease-related pathology, synapse protection, and up-regulation of nerve cells via multiple signaling pathways.

Role of natural products for the treatment of Alzheimer's disease.

Negative psychological and physiological consequences of neurodegenerative disorders represent a high social and health cost. Among the neurodegenerative disorders Alzheimer's disease (AD) is recognized as a leading neurodegenerative condition and a primary cause of dementia in the elderlys. AD is considered as neurodegenerative disorder that progressively impairs cognitive function and memory. According to current epidemiological data, about 50 milLion people worldwide are suffering from AD. The primary symptoms of AD are almost inappreciable and usually comprise forgetfulness of recent events. Numerous processes are involved in the development of AD, for example oxidative stress (OS) mainly due to mitochondrial dysfunction, intracellular the accumulation of hyperphosphorylated tau (τ) proteins in the form of neurofibrillary tangles, excessive the accumulation of extracellular plaques of beta-amyloid (Aß), genetic and environmental factors. Running treatments only attenuate symptoms and temporarily reduce the rate of cognitive progression associated with AD. This means that most treatments focus only on controlLing symptoms, particularly in the initial stages of the disease. In the past, the first choice of treatment was based on natural ingredients. In this sense, diverse natural products (NPs) are capable to decrease the symptoms and alleviate the development of several diseases including AD attracting the attention of the scientific community and the pharmaceutical industry. Specifically, numerous NPs including flavonoids, gingerols, tannins, anthocyanins, triterpenes and alkaloids have been shown anti-inflammatory, antioxidant, anti-amyloidogenic, and anti-choLinesterase properties. This review provide a summary of the pathogenesis and the therapeutic goals of AD. It also discusses the available data on various plants and isolated natural compounds used to prevent and diminish the symptoms of AD.

Daidzein Pro-cognitive Effects Coincided with Changes of Brain Neurotensin1 Receptor and Interleukin-10 Expression Levels in Obese Hamsters.

At present, concerns are pointing to "tasteful" high-fat diets as a cause of conditioning physical-social states that through alterations of some key emotional- and nutritional-related limbic circuits such as hypothalamic and amygdalar areas lead to obesity states. Feeding and energetic homeostatic molecular mechanisms are part of a complex neuronal circuit accounting for this metabolic disorder. In an attempt to exclude conventional drugs for treating obesity, daidzein, a natural glycosidic isoflavone, which mimics estrogenic neuroprotective properties against increased body weight, is beginning to be preferred. In this study, evident anxiolytic-like behaviors were detected following treatment of high-fat diet hamsters with daidzein as shown by extremely evident (p < 0.001) exploration tendencies in novel object recognition test and a notably greater amount of time spent (p < 0.01) in open arms of elevated plus maze. Moreover, the isoflavone promoted a protective role against neurodegeneration processes as shown by few, if any, amino cupric silver granules in amygdalar, hypothalamic and hippocampal neuronal fields when compared with obese hamsters. Interestingly, elevated expression levels of the anorexic neuropeptide receptor neurotensin1 in the above limbic areas of obese hamsters were extremely reduced by daidzein, especially during recovery of cognitive events. Contextually, such effects were strongly paralleled by increased levels of the anti-neuroinflammatory cytokine, interleukin-10. Our results corroborate a neuroprotective ability of this natural glycosidic isoflavone, which through its interaction with the receptor neurotensin1 and interleukin-10 pathways is correlated not only to improved feeding states, and subsequently obesity conditions, but above all to cognitive performances.

Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities.

ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.

Zingiber officinale ameliorates Alzheimer's disease and Cognitive Impairments: Lessons from preclinical studies.

Alzheimer's disease (AD) is a neurodegenerative condition mostly communal in people of advanced years accompanying various dysfunctionalities especially cognitive impairments. A number of cellular damages, such as amyloid-beta aggregation, tau protein hyperphosphorylation, some neurotransmitter imbalances, apoptosis, oxidative stress, and inflammatory responses are responsible for AD incidence. As a reason for inadequate efficacy, side effects, and pharmacokinetic problems of conventional drugs used for AD, the discovery of novel therapeutic agents with multi-targeted potential is desirable. Protective properties of phytochemicals combat numerous diseases and their vast acceptance and demand in human beings encouraged scientists to assess their effective activities. Zingiber officinale, gingerol, shogaol, and borneol were evaluated against memory impairments. Online databases including; Web of Science, Scopus, Embase, Pubmed, ProQuest, ScienceDirect, and Cochrane Library were searched until 3th February 2020. In vitro, in vivo, and clinical studies are included after screening their eligibility. Mostly interventive mechanisms such as; oxidative stress, neuroinflammation, and apoptosis are described. Correlation between the pathogenesis of AD and signaling pathways is explicated. Results and scores of cognition measurements are clarified due to in vivo studies and clinical trials. Some traditional aspects of consuming ginger in AD are also mentioned in the present review. In accumulation ginger and its components possess great potency for improving and abrogating memory dysfunctions but conducting further studies to evaluate their pharmacological and pharmaceutical aspects is required.

Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review.

PURPOSE: Parkinson disease (PD) medications are not readily available in all countries. Citicoline increases dopamine synthesis and inhibits dopamine uptake. This systematic review aims to synthesize current existing evidence on the efficacy of citicoline adjunctive therapy in improving PD symptoms. METHODS: An extensive literature search of Scopus, Embase, PubMed, Cochrane Library, and Google Scholar was conducted for articles published on or before December 31, 2019. The studies were screened and selected by 2 independent reviewers. We included all studies that explored the efficacy of citicoline as an adjunct therapy in PD. FINDINGS: A total of 7 studies (2 crossover, 3 randomized controlled, and 2 open prospective studies) were included. Despite the varied outcome tools, this review found that patients with PD who were taking citicoline had significant improvement in rigidity, akinesia, tremor, handwriting, and speech. Citicoline allowed effective reduction of levodopa by up to 50%. Significant improvement in cognitive status evaluation was also noted with citicoline adjunctive therapy. IMPLICATIONS: Citicoline adjuvant therapy has beneficial effects as an adjuvant therapy in patients with PD. However, due to the heterogeneity of the studies, there is a need for more high-quality studies.

Marinoid J, a phenylglycoside from Avicennia marina fruit, ameliorates cognitive impairment in rat vascular dementia: a quantitative iTRAQ proteomic study.

CONTEXT: Fruit of Avicennia marina (Forsk.) Vierh. (Acanthaceae) is used as a Chinese herb. Studies have found that it contains marinoid J, a novel phenylethanoid glycoside (PG) compound, but its neuroprotective functions are largely unknown. OBJECTIVE: This study evaluated the effects of marinoid J on vascular dementia (VD) and determined its potential mechanisms of action. MATERIALS AND METHODS: The VD model was established by the ligation of the bilateral common carotid artery in Sprague-Dawley rats, who received daily intragastrically administration of saline, marinoid J (125 or 500 mg/kg body weight/d), or oxiracetam (250 mg/kg body weight/d) for 14 days (20 rats in each group). The Morris water maze (MWM) was used to evaluate cognitive performance. The hippocampus was subjected to histological and proteomic analyses. RESULTS: Marinoid J shortened the escape latency of VD rats (31.07 ± 3.74 s, p < 0.05). It also decreased malondialdehyde (MDA) (27.53%) and nitric oxide (NO) (20.41%) while increasing superoxide dismutase (SOD) (11.26%) and glutathione peroxidase (GSH-Px) (20.38%) content in hippocampus tissues. Proteomic analysis revealed 45 differentially expressed proteins (DEPs) in marinoid J-treated VD rats, which included angiotensin-converting enzyme (ACE), keratin 18 (KRT18), cluster of differentiation 34 (CD34), and synaptotagmin II (SYT2). CONCLUSIONS: Marinoid J played a role in protecting hippocampal neurons by regulating a set of proteins that influence oxidative stress and apoptosis, this effect may thereby alleviate the symptoms of VD rats. Thus, pharmacological manipulation of marinoid J may offer a novel opportunity for VD treatment.

The effect of scalp electroacupuncture combined with Memantine in patients with vascular dementia: A retrospective study.

Currently there is no effective treatment for vascular dementia (VaD). Pharmacological treatment often lead to severe complications and require drug dosage adjustment. This study investigated the effect of scalp electroacupuncture combined with Memantine in VaD. The safety and antioxidative effect of scalp electroacupuncture were also explored.A retrospective study was conducted and data of inpatients of Linyi Central Hospital with VaD between June 2017 and May 2018 were collected and sorted. The patients were divided into scalp electroacupuncture-medication (A), scalp electroacupuncture (B) and medication (control) (C) groups, in which Memantine was prescribed as medication. Cognitive function, activities of daily living and quality of life assessed by Montreal Cognitive Assessment (MoCA), Barthel index and dementia quality of life questionnaire; the contents of superoxide dismutase, lipid peroxide and nitric oxide in blood samples; and adverse reaction were compared.Data from a total of 150 patients were collected (Group A, n = 55; Group B, n = 50; Group C, n = 45). The post-treatment/follow-up Montreal Cognitive Assessment, Barthel index and dementia quality of life questionnaire scores were significantly improved in all groups compared to pre-treatment (groups A and B, P<.01; group C, P<.05). The improvements were significant for groups A vs C, B vs C (P<0.01, both), and group A vs B (P<.05). The post-treatment/follow-up levels of lipid peroxide and nitric oxide decreased significantly while superoxide dismutase increased significantly in groups A and B compared to pre-treatment (P<.01, both). The differences were significant for groups A vs C, and B vs C (P < .01, both), but not significant between groups A and B (P > .05). There were no significant adverse events occurred during the study and follow-up.In combined treatment, scalp electroacupuncture works in parallel with Memantine and significantly increase the therapeutic effect in VaD with no significant adverse events. Scalp electroacupuncture may have the potential to serve as an option or alternative treatment for VaD. Scalp electroacupuncture may alleviate VaD symptoms through its antioxidative mechanism.

5-N-ethyl Carboxamidoadenosine Stimulates Adenosine-2b Receptor-Mediated Mitogen-Activated Protein Kinase Pathway to Improve Brain Mitochondrial Function in Amyloid Beta-Induced Cognitive Deficit Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with loss in memory as one of the cardinal features. 5-N-ethyl carboxamidoadenosine (NECA), an agonist of adenosine-2b receptor, exerts neuroprotective activity against several experimental conditions. Further, NECA activates mitogen-activated protein kinase (MAPK) and also attenuates mitochondrial toxicity in mammalian tissues other than brain. Moreover, there is no report on the role of A2b/MAPK-mediated signaling pathway in Aß-induced mitochondrial toxicity in the brain of the experimental animals. Therefore, the present study evaluated the neuroprotective activity of NECA with or without MAPK inhibitor against Aß-induced cognitive deficit and mitochondrial toxicity in the experimental rodents. Further, the effect of NECA with or without MAPK inhibitor was evaluated on Aß-induced mitochondrial toxicity in the memory-sensitive mice brain regions. Intracerebroventricular (ICV) injection of Aß 1-42 was injected to healthy male mice through Hamilton syringe via polyethylene tube to induce AD-like behavioral manifestations. NECA attenuated Aß-induced cognitive impairments in the rodents. In addition, NECA ameliorated Aß-induced Aß accumulation and cholinergic dysfunction in the selected memory-sensitive mouse HIP, PFC, and AMY. Further, NECA significantly attenuated Aß-induced mitochondrial toxicity in terms of decrease in the mitochondrial function, integrity, and bioenergetics in the brain regions of these animals. However, MAPKI diminished the therapeutic effects of NECA on behavioral, biochemical, and molecular observations in AD-like animals. Therefore, it can be speculated that NECA exhibits neuroprotective activity perhaps through MAPK activation in AD-like rodents. Moreover, A2b-mediated MAPK activation could be a promising target in the management of AD.

The nootropic and anticholinesterase activities of Clitoria ternatea Linn. root extract: Potential treatment for cognitive decline.

BACKGROUND: Clitoria ternatea (CT) is an herbal plant that has been used as a memory booster in folk medicine. CT root extract has been proven to restore chronic cerebral hypoperfusion (CCH)-induced memory deficits in a rat model, but the underlying mechanisms and the toxicity profile following repeated exposure have yet to be explored. THE AIM OF THE STUDY: To investigate the effects of the chronic (28 days) oral administration of CT root extract on CCH-induced cognitive impairment, neuronal damage and cholinergic deficit, and its toxicity profile in the CCH rat model. MATERIALS AND METHODS: The permanent bilateral occlusion of common carotid arteries (PBOCCA) surgery method was employed to develop a CCH model in male Sprague Dawley (SD) rats. Then, these rats were given oral administration of CT root extract at doses of 100, 200, and 300 mg/kg, respectively for 28 days and subjected to behavioural tests. At the end of the experiment, the brain was harvested for histological analysis and cholinesterase activities. Then, blood samples were collected and organs such as liver, kidney, lung, heart, and spleen were procured for toxicity assessment. RESULTS: Chronic treatment of CT root extract at doses of 200 and 300 mg/kg, restored memory impairments induced by CCH. CT root extract was also found to diminish CCH-induced neuronal damage in the CA1 region of the hippocampus. High dose (300 mg/kg) of the CT root extract was significantly inhibited the increased acetylcholinesterase (AChE) activity in the frontal cortex and hippocampus of the PBOCCA rats. In toxicity study, repeated doses of CT root extract were found to be safe in PBOCCA rats after 28 days of treatment. CONCLUSIONS: Our findings provided scientific evidence supporting the therapeutic potential of CT root extract in the treatment of vascular dementia (VaD)-related cholinergic abnormalities and subsequent cognitive decline.

Perinatal encephalopathy, the syndrome of intracranial hypertension and associated diagnostic labels in the Commonwealth of Independent States: a systematic review.

BACKGROUND: The WHO reports excessive rates of ill-defined neurological diagnoses and ineffective and potentially harmful drug treatments in children in the Commonwealth of Independent States (CIS). Collectively termed perinatal encephalopathy and the syndrome of intracranial hypertension (PE-SIH), these diagnoses are important contributors to perceived childhood morbidity and disability in the CIS. A systematic compilation of information on PE-SIH is lacking. METHODS: We systematically reviewed publications between 1970 and 2020 on PE-SIH in Azerbaijani, English, Russian and Ukrainian languages and summarised information on PE-SIH. RESULTS: We identified 30 publications (70% in Russian) published 1976-2017. The diagnosis of PE-SIH was either based on unreported criteria (67% of reports), non-specific clinical features of typically developing children or those with common developmental disorders (20% of reports) or cranial ultrasound (13% of reports). The reported proportion of children with PE-SIH in the study samples ranged from 31% to 99%. There were few published studies on reassessments of children diagnosed with PE-SIH, and these did not confirm neurological disease in the majority of children. Treatments included multiple unlicenced drugs without established effectiveness and with potential unwanted effects. CONCLUSION: This review suggests that PE-SIH is a medical diagnostic label that is used in numerous children without substantive associated disease. The diagnosis and treatment of PE-SIH is a multidimensional, iatrogenic, clinical and public health problem in the CIS. With increasing use of evidence-based medicine guidelines in the region, it is hoped that PE-SIH will gradually disappear, but actions to accelerate this change are nevertheless needed.

Bacopa monnieri (L.) Wettst. Extract Improves Memory Performance via Promotion of Neurogenesis in the Hippocampal Dentate Gyrus of Adolescent Mice.

Bacopa monnieri L. Wettst. (BM) is a botanical component of Ayurvedic medicines and of dietary supplements used worldwide for cognitive health and function. We previously reported that administration of BM alcoholic extract (BME) prevents trimethyltin (TMT)-induced cognitive deficits and hippocampal cell damage and promotes TMT-induced hippocampal neurogenesis. In this study, we demonstrate that administration of BME improves spatial working memory in adolescent (5-week- old) healthy mice but not adult (8-week-old) mice. Moreover, improved spatial working memory was retained even at 4 weeks after terminating 1-week treatment of adolescent mice. One-week BME treatment of adolescent mice significantly enhanced hippocampal BrdU incorporation and expression of genes involved in neurogenesis determined by RNAseq analysis. Cell death, as detected by histochemistry, appeared not to be significant. A significant increase in neurogenesis was observed in the dentate gyrus region 4 weeks after terminating 1-week treatment of adolescent mice with BME. Bacopaside I, an active component of BME, promoted the proliferation of neural progenitor cells in vitro in a concentration-dependent manner via the facilitation of the Akt and ERK1/2 signaling. These results suggest that BME enhances spatial working memory in healthy adolescent mice by promoting hippocampal neurogenesis and that the effects of BME are due, in significant amounts, to bacopaside I.