Donepezil Research Articles

Donepezil for Fatigue and Psychological Symptoms in Post–COVID-19 Condition

ImportanceFatigue is the most commonly reported symptom of post–COVID-19 condition (also known as long COVID) and impairs various functions. One of the underlying mechanisms may be intracerebral inflammation due to decreases in acetylcholine levels.ObjectiveTo examine the effects of donepezil hydrochloride, an acetylcholinesterase inhibitor, on post–COVID-19 fatigue and psychological symptoms.Design, Setting, and ParticipantsA multicenter, double-blind randomized clinical trial was performed in Japan. Between December 14, 2022, and March 31, 2024, adult patients within 52 weeks of the onset of COVID-19 and with a global binary fatigue score of 4 or greater on the Chalder Fatigue Scale were randomized into a donepezil or a placebo group.ExposureThe intervention was conducted during a 3-week period, with donepezil hydrochloride being administered at a dosage of 3 mg/d for the first week and then 5 mg/d for 2 weeks.Main Outcomes and MeasuresThe primary outcome was a change in the Chalder Fatigue Scale score and the absolute score 3 weeks after the initiation of treatment. Other outcomes at 3 and 8 weeks, such as psychological symptoms and quality of life, were evaluated as secondary outcomes.ResultsA total of 120 eligible patients were enrolled and 10 withdrew or were lost to follow-up; therefore, 110 patients (55 in each group) were included in the efficacy analysis (64 [58%] female; mean [SD] age, 43 [12] years). No significant differences were observed in baseline characteristics between the 2 groups. The baseline-adjusted estimating treatment effect of donepezil, measured as the mean difference on Chalder Fatigue Scale scores at 3 weeks, was 0.34 (95% CI, −2.23 to 2.91), showing no significant effect of the intervention (P = .79). Scores for the Hospital Anxiety and Depression Scale, Impact of Event Scale–Revised, EuroQol 5-Dimension 5-Level Version, Patient Health Questionnaire, and Daily Health Status at 3 and 8 weeks were similar. No serious adverse events occurred in either group.Conclusions and RelevanceIn this randomized clinical trial of donepezil to treat post–COVID-19 condition, the efficacy for fatigue and psychological symptoms was not confirmed in a general population. The development of effective therapeutics for post–COVID-19 symptoms is needed, and more clinical trials should be conducted in the future.Trial RegistrationJapan Registry of Clinical Trials Identifier: jRCT 2031220510

Lancao decoction alleviates Alzheimer's disease: Depending on activating CaMKII to protect neuronal refunction by reducing β-amyloid in the hippocampus.

Lancao decoction alleviates Alzheimer's disease: Depending on activating CaMKII to protect neuronal refunction by reducing β-amyloid in the hippocampus.

Donepezil Reverses Alcohol-Induced Changes in Hippocampal Neurogenic and Glial Responses FollowingAdolescent Intermittent Ethanol ExposureIntoAdulthood in Female Rats.

Adolescent intermittent ethanol (AIE) exposure leads to persisting increases in glial markers and significantly decreases the neurogenic niche in the dentate gyrus of the hippocampus. Our previous study indicated that donepezil (DZ), a cholinesterase inhibitor, can reverse the AIE effect of decreased doublecortin (DCX), a neurogenic marker, and increased cleaved caspase 3, a marker of apoptosis, in the dentate gyrus of male rats. However, to date, no studies have assessed the effects of DZ on AIE effects in females. The purpose of this study was to determine whether DZ can reverse neuroimmune, neurogenic, and neuronal death effects in adulthood after AIE in female rats. Adolescent female rats were given 14 doses of ethanol (5 g/kg) over 24 days by intragastric gavage. Seventeen days later, DZ (2.5 mg/kg, 1.88 mL/kg, i.g., in water) was then administered daily for 4 days prior to sacrifice. Immunohistochemical techniques were utilized to determine the effects of DZ on AIE-induced changes in neurogenesis, cell death, glial, and neuroimmune markers. As expected, AIE decreased the neurogenic markers DCX, SOX2, and Ki-67 in the dentate gyrus and also caused an increase in the glial markers GFAP and Iba-1 in the hippocampus. The effects of AIE on neurogenic and glial markers were reversed by DZ treatment, but the reversal of AIE effects on glial markers was regionally specific within the hippocampus. Overall, these findings indicate that systemic DZ in adult female rats ameliorates the effects of AIE on neurogenesis, neuronal cell death, neuroimmune markers, and glial activation markers. Future studies will determine if DZ alters hippocampally driven behaviors, as well as the mechanisms underlying donepezil's effects.

Efficacy of Sodium Oligomannate Capsules Combined with Memantine Hydrochloride and Donepezil Hydrochloride in Treating Moderate Alzheimer’s Disease

Objective: To explore the clinical efficacy of sodium oligomannate capsules combined with memantine hydrochloride and donepezil hydrochloride in the treatment of moderate Alzheimer’s disease (AD) and analyze its impact on cognitive function. Methods: Eighty patients with moderate AD admitted to the neurology outpatient clinic of our hospital from June 2021 to December 2022 were selected as the study subjects and randomly divided into a study group and a control group, each with 40 patients. The control group was treated with oral memantine hydrochloride and donepezil hydrochloride, while the study group was additionally treated with oral sodium oligomannate capsules for 24 weeks. The scores of neuropsychological scales [Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE)], and Activities of Daily Living (ADL) scale were compared before and after treatment. Additionally, the levels of homocysteine (Hcy), central nervous system-specific protein (S100-β), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were measured in both groups, and the treatment effects and adverse reactions were compared. Results: After 24 weeks of treatment, the MMSE, MoCA, and ADL scores of both groups were significantly higher than those before treatment (P < 0.05). Compared with the control group after 24 weeks of treatment, the study group had significantly higher MMSE, MoCA, and ADL scores (P < 0.05), and significantly lower levels of Hcy, IL-6, and TNF-α (P < 0.05). Both the study group and the control group showed reduced levels of Hcy, IL-6, and TNF-α after 24 weeks of treatment compared to before (P < 0.05), but there was no significant change in S100-β levels (P > 0.05). Conclusion: The combination of sodium oligomannate capsules, memantine hydrochloride, and donepezil hydrochloride is effective in the treatment of moderate AD. It can improve the cognitive function and daily living abilities of patients with dementia, enhancing their quality of life.

Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer's and Parkinson's Diseases.

Alzheimer's and Parkinson's are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates and the progressive and permanent loss of neurons are the major characteristic features of these disorders. Although the precise mechanisms causing Alzheimer's disease (AD) and Parkinson's disease (PD) are still unknown, there is a wealth of evidence suggesting that misfolded proteins, accumulation of misfolded proteins, dysfunction of neuroreceptors and mitochondria, dysregulation of enzymes, and the release of neurotransmitters significantly influence the pathophysiology of these diseases. There is no effective protective medicine or therapy available even with the availability of numerous medications. There is an urgent need to create new and powerful bioactive compounds since the number of people with NDDs is rising globally. Heterocyclic compounds have consistently played a pivotal role in drug discovery due to their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine hydrochloride, and opicapone, feature heterocyclic cores. As these heterocyclic compounds have exceptional therapeutic potential, heterocycles are an intriguing research topic for the development of new effective therapeutic drugs for PD and AD. This review aims to provide current insights into the development and potential use of heterocyclic compounds targeting diverse therapeutic targets to manage and potentially treat patients with AD and PD.

Tangeretin offers neuroprotection against colchicine-induced memory impairment in Wistar rats by modulating the antioxidant milieu, inflammatory mediators and oxidative stress in the brain tissue

BackgroundTangeretin, a flavone compound (O-polymethoxylated) naturally present in tangerine and other citrus peels has demonstrated effectiveness as an anti-inflammatory and neuroprotective agent in several disease model. This study evaluated the impact of tangeretin in mitigating cognitive dysfunction and oxidative stress induced by colchicine in rats, comparing its efficacy with donepezil hydrochloride.MethodsCognitive dysfunction was induced by administering colchicine (15 µg/rat) intracerebroventricularly (ICV) via a stereotaxic apparatus in male Wistar rats. Colchicine resulted in poor memory retention in acquiring and retaining a spatial navigation task, passive avoidance apparatus, and Morris water maze paradigms. Chronic treatment with tangeretin (at doses of 50, 100, and 200 mg/kg, p.o. once daily) and donepezil hydrochloride (at a dose of 10 mg/kg, p.o. daily) for 28 days, starting seven days before colchicine injection, significantly ameliorated colchicine-induced cognitive impairment.ResultsThe biochemical analysis showed that chronic administration of tangeretin effectively reversed the colchicine-induced increase in the level/activity of lipid peroxidation, hydrogen peroxide (H2O2), myeloperoxidase (MPO), nitrite, reactive oxygen species (ROS), tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), serotonin, dopamine, glutamate, amyloid beta (Aβ) peptide, and caspase-3. Tangeretin also reversed the colchicine-induced reduction in the level/activity of brain-derived neurotrophic factor (BDNF), amma-aminobutyric acid (GABA), acetylcholinesterase (AChE), glutathione S-Transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and total thiol (T-SH) in rat brains. However, donepezil hydrochloride did not prevent oxidative stress.ConclusionsThese findings suggest that chronic administration of tangeretin at 50, 100, and 200 mg/kg, p.o. once daily, was protective in mitigating colchicine-induced cognitive impairment and associated oxidative stress. At the same time, donepezil hydrochloride did not demonstrate similar effects.

Optimizing Neuroprotective Nano-structured Lipid Carriers for Transdermal Delivery through Artificial Neural Network.

Dementia associated with Alzheimer's disease (AD) is a neurological disorder. AD is a progressive neurodegenerative condition that predominantly impacts the elderly population, although it can also manifest in younger people through the impairment of cognitive functions, such as memory, cognition, and behaviour. Donepezil HCl and Memantine HCl are encapsulated in Nanostructured Lipid Carriers (NLCs) to prolong systemic circulation and minimize the systemic side effects. This work explores the use of data mining tools to optimize the formulation of NLCs comprising of Donepezil HCl and Memantine HCl for transdermal drug delivery. Neuroprotective drugs and excipients are utilized for protecting the nervous system against damage or degeneration. The NLCs were formulated using a high-speed homogenization technique followed by ultrasonication. NLCs were optimized using Box Behnken Design (BBD) in Design Expert Software and artificial neural network (ANN) in IBM SPSS statistics. The independent variables included the ratio of solid lipid to liquid lipid, the percentage of surfactant, and the revolutions per minute (RPM) of the high-speed homogenizer. The NLCs that were formulated had a mean particle size ranging from 67.0±0.45 to 142.4±0.52 nm. Both drugs have a %EE range over 75%, and Zeta potential was determined to be - 26±0.36 mV. CryoSEM was used to do the structural study. The permeation study showed the prolonged release of the formulation. The results indicate that NLCs have the potential to be a carrier for transporting medications to deeper layers of the skin and reaching systemic circulation, making them a suitable formulation for the management of Dementia. Both ANN and BBD techniques are effective tools for systematically developing and optimizing NLC formulation.

Developing multifaceted drug synergistic therapeutic strategy against neurological disorders.

Developing multifaceted drug synergistic therapeutic strategy against neurological disorders.

Effect of Social Restriction Due to the COVID-19 Pandemic on Activity of Daily Living and Disease Severity of Patients With Alzheimer Disease: Sub-analysis of a Double-blinded Noninferiority Study of Donepezil Patches and Donepezil Tablets.

We previously reported that social restrictions due to the COVID-19 pandemic led to a decline in cognitive function in patients with Alzheimer disease (AD). Here, we assessed the effects of COVID-19 restrictions on the activities of daily living (ADL) and disease severity in patients by comparing them to a control group. We examined the impact on ADL, evaluated using disability assessment for dementia (DAD), and disease severity, evaluated using the ABC dementia scale, in patients with mild-to-moderate AD. We conducted a post hoc subgroup analysis of a double-blinded, noninferiority study of donepezil 27.5mg patches and donepezil hydrochloride 5mg tablets (JapicCTI-194582). After showing the noninferiority of both treatments, we combined the data from both groups for analysis. The subpopulation of the per-protocol set grouped by completing the double-blinded evaluation before and on/after the mild lockdown was balanced (n=136 and n=120). Patient demographics were similar between the subgroups. The decline in the DAD and ABC dementia scale scores [least-squares mean (SE)] was ameliorated by social restriction [-3.810 (0.743) and -1.871 (0.697) and -1.147 (0.285) and -0.419 (0.267), respectively (not significant)]. Normalcy and expectation biases can affect the evaluation of ADL and disease severity by caregivers under high stress and deterioration of mental conditions.

Assessment of greenness, blueness, and whiteness profiles of a validated HPLC-DAD method for quantitation of Donepezil HCl and Curcumin in their laboratory prepared co-formulated nanoliposomes

White and Green Analytical Chemistry are innovative approaches in analytical chemistry that prioritize both sustainability and efficiency. Together, these approaches aim to advance scientific research while minimizing environmental impact and enhancing safety. This integration of environmental consciousness into analytical practices represents a significant step forward in achieving sustainable scientific progress. In the present study, a sensitive eco-friendly HPLC-DAD method was carried out and validated to allow concurrent determination of Donepezil HCl (DPZ) and Curcumin (CUR) in their pure form and laboratory made nano-liposome formulation. Optimum seperation was accomplished by utilising Zobrax Eclipse Plus C18 column (4.6*100 mm,5 μm) with gradient elution of the mobile phase composed of 0.02 M phosphate buffer at pH 3.2 and ethanol at flow rate of 1.5 ml/min. A diode array detector (DAD) was implemented for detection at 273 nm and 435 nm for DPZ and CUR, respectively, with the column oven set at 40 °C. The method was validated according to ICH specifications in terms of accuracy, precision, linearity range, detection and quantification limit. The calibration plots were linear with correlation coefficients (r2) = 0.999 over the range (0.1–100 µg/ml) and (0.1–100 µg/ml) for DPZ and CUR, successively. The validated HPLC-DAD approach was adopted to analyse both medications in laboratory prepared nano-liposomal formulation in which the analytes were successfully quantified with good recovery values and no disrubtion from the added excipients. The investigation of whiteness, blueness, and greenness metrics revealed a major benefit of the suggested approach over previous reported ones.

Blackcurrant (Ribes nigrum L.) and Its Association with Donepezil Restore Cognitive Impairment, Suppress Oxidative Stress and Pro-inflammatory Responses, and Improve Purinergic Signaling in a Scopolamine-Induced Amnesia Model in Mice.

Purinergic signaling plays a major role in aging and neurodegenerative diseases, which are associated with memory decline. Blackcurrant (BC), an anthocyanin-rich berry, is renowned for its antioxidant and neuroprotective activities. However, evidence on the effects of BC on purinergic signaling is lacking. This study investigated the effects of BC and its association with Donepezil (DNPZ) on learning and memory, on the modulation of purinergic signaling, pro-inflammatory responses, and oxidative markers in a mouse model of cognitive impairment chronically induced by scopolamine (SCO). Animals were divided into twelve groups and treated with BC (50 or 100mg/kg), and/or DNPZ (5mg/kg), and/or SCO (1mg/kg). Results showed that SCO decreased spatial learning and memory as assessed by the Morris Water Maze test, and treatment with BC and/or DNPZ restored these effects. Furthermore, BC and/or DNPZ treatments also prevented changes in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase (ADA) activities and restored the increased density of P2X7 and A2A receptors in synaptosomes of the cerebral cortex of SCO-induced mice. Moreover, the increased Nod-like receptor protein 3 (NLRP3) and interleukin-1β expression, and the oxidative stress markers levels were reduced by BC and/or DNPZ treatments, compared with the SCO group. Overall, BC and/or DNPZ treatments ameliorated SCO-induced cognitive decline, alleviated oxidative stress and pro-inflammatory responses, and improved purinergic signaling. These findings underscore the potential of BC, especially when in combination with DNPZ, as a therapeutic agent for the prevention of memory deficits associated with aging or neurological diseases.

Formulation Design of Orally Disintegrating Film Using Two Cellulose Derivatives as a Blend Polymer.

Background/Objectives: Orally disintegrating film (ODF) is prepared using water-soluble polymers as film-forming agents. To improve mechanical and disintegration properties, some polymers need to be blended with others. This study aimed to investigate the utility of hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC) as blend film-forming components for ODFs. Methods: Placebo ODFs were prepared using polymer mixtures with blend ratios ranging from 20% to 80% HPC with HPMC. Mechanical properties, including tensile strength, elastic modulus, elongation at break, and folding endurance, as well as disintegration times, were evaluated. Additionally, blend films incorporating donepezil hydrochloride (DH) as a model active pharmaceutical ingredient (API) were prepared and assessed to determine their mechanical properties and disintegration behavior. Results: Blend films were successfully formed using HPMC/HPC solutions. The 40/60 and 20/80 HPMC/HPC blends exhibited the lowest mechanical strength and elongation, whereas blends containing more than 40% HPC demonstrated shorter disintegration times. Films with DH were successfully formed, though the addition of DH reduced tensile strength and elongation. The decline in mechanical properties was mitigated in HPMC/HPC blend films. Our results, including DSC and FTIR results, led us to conclude that the HPMC/HPC blend films were micro-immiscible, but they were macro-miscible when the amount of the minor component was sufficiently small. Conclusions: HPMC/HPC blends in appropriate ratios are effective as film-forming polymers for ODFs. The addition of DH impacts the mechanical properties, but the decline is less pronounced when using HPMC/HPC blends.

Dimethysiloxane polymer for the effective transdermal delivery of donepezil in Alzheimer's disease treatment.

Donepezil (DNZ) has been used to treat dementia associated with mild, moderate, or severe Alzheimer's disease (AD). DNZ uptake can alleviate cognitive symptoms in AD patients via acetylcholinesterase (AChE) inhibition. However, oral administration of DNZ has limitations, including first-pass metabolism, difficulties with swallowing, and low patient compliance. In this work, we disclose a novel transdermal DNZ delivery system utilizing T2 polymer, synthesized via the ring-opening polymerization of 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane with trifluoroacetic acid (TFA). In the in vivo studies in an AD animal model, the DNZ-loaded T2 polymer (DNZ@T2) facilitated efficient transdermal DNZ delivery to the bloodstream and improved spatial working memory and long-term memory of the AD mouse model. Both the T2 polymer and DNZ@T2 exhibited low cytotoxicity and non-significant in vivo toxicity. This research highlights a promising transdermal delivery strategy for AD treatment, potentially enhancing therapeutic efficacy and patient compliance.

Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy

Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy

Effect of Artesunate on Behavioral Functions in Experimental Model of Alzheimer’s Disease

ABSTRACT Introduction: Alzheimer’s disease (AD) is a common form of dementia, causing loss of memory and cognitive impairment because of progressive neurodegeneration. Current treatment modalities for AD do not cure the disease completely, are expensive, and are associated with numerous adverse effects. Artesunate is a semisynthetic product of artemisinin, derived from the plant Artemisia annua and used conventionally to fight malaria for a long time in Chinese medicine. Artesunate is a multipotent agent with a wide array of actions. Methodology: The study was conducted in the animal house of the Department of Pharmacology, KIMS, Bhubaneswar, after getting approval from the Institutional Animal Ethics Committee. A total of 36 albino Wistar rats weighing 150–200 gms were selected for the study and divided into six groups containing six rats each. Group I was the normal control, and rats received only normal saline and regular food, whereas group II rats were disease control and received aluminum chloride only. Group III rats were the standard control group and received donepezil hydrochloride along with aluminum chloride, whereas groups IV, V, and VI were the test treatment control group receiving graded doses of artesunate along with aluminum chloride. The behavioral parameters were assessed through the morris water maze, elevated plus maze, actophotometer, and passive avoidance tests. Results: Artesunate treatment group showed considerable improvement in behavioral functions, and this effect was comparable with a standard group at the highest selected dose. Conclusion: Artesunate demonstrated neuroprotective effects through various possible mechanisms. Hence, artesunate might be therapeutically useful in neurogenerative disorders.

Effect of Eucommiae Cortex extract mediated by ERβ/JNK pathway on learning and memory ability of APP/PS1 double-transgenic mice

To study the ameliorative effect of Eucommiae Cortex extract on spatial learning disabilities in APP/PS1 double-transgenic mice and explore its relationship with estrogen receptor β(ERβ)/c-Jun N-terminal kinase(JNK) signaling pathway, sixty 3-month-old male APP/PS1 mice were randomly divided into a model group, an anti-brain failure capsule group(0.585 g·kg~(-1)), a donepezil hydrochloride group(0.65 mg·kg~(-1)), and a Eucommiae Cortex extract group(1.3 g·kg~(-1)), and 15 C57BL/6 mice of the same genetic background were set as WT control group. The learning and memory ability of mice was assessed by the Morris water maze test(MWM), the passive avoidance test(PAT), and the novel object recognition test(NOR). The histomorphological and cellular ultrastructural features of the hippocampal region of the mice were observed by hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM); the molecular docking validation of the key active ingredients and the key targets was performed by using AutoDock Vina software, and the immunohistochemical method(IHC) was used to detect the ERβ expression in the dentate gyrus(DG) area of mouse hippocampus. Western blot(WB) was utilized to detect the expression of ERβ, p-JNK, and JNK in mouse hippocampal area. Compared with those in the WT control group, the results of behavioral experiments showed that the latency of the mice in the model group was significantly increased, the number of platform traversals, and the target quadrant residence time were significantly decreased in the MWM. The evasion latency was significantly reduced, and the number of errors was significantly increased in the PAT. The index of recognition of novel objects was significantly reduced in the NOR. The results of HE staining indicated that the hippocampal area of mice in the model group showed a decrease in the number of neurons, disorganization of pyramidal cell arrangement, nucleus consolidation, and other changes. TEM results showed that some neuronal nuclei in the hippocampal area had a consolidated state, slightly thickened and aberrant nuclear membranes, and fewer intracytoplasmic nidus bodies; the IHC results showed that the expression of ERβ in the hippocampal DG area of the mice was reduced. The WB results showed that the ERβ expression in the hippocampal tissue was decreased, and the p-JNK/JNK level was elevated. Compared with the model group, the Eucommiae Cortex extract group showed a significant decrease in latency, and increase in number of platform traversals and target quadrant residence time in the MWM, a significant increase in evasion latency and decrease in number of errors in the PAT, and a significant increase in the index of recognition of novel objects in the NOR. In addition, there was an increase in the number of neurons in the hippocampal area of mice. The pyramidal cells tended to be arranged in an orderly manner; the nuclei of neurons in the hippocampal area were in a better state; the expression of ERβ in the hippocampal DG area of the mice was elevated; the expression of ERβ in the hippocampal tissue was elevated, and the level of p-JNK/JNK was reduced. The effects of donepezil hydrochloride group and anti-brain failure capsule on APP/PS1 mice in terms of behavioral, HE, and TEM indexes were similar to those of Eucommiae Cortex extract, and there was no significant difference between donepezil hydrochloride group and the model group in IHC and WB experiments, and the results of molecular docking indicated that the estrogen-like components in Eucommiae Cortex extract were tightly bound to ERβ. In conclusion, the binding of Eucommiae Cortex extract to estrogen receptors, regulation of ERβ expression, and activation of ERβ/JNK signaling pathway may be one of the key mechanisms by which it improves the learning and memory ability of APP/PS1 mice.

Development of pH‐Responsive Hydrogel Excipient From Karaya Gum for Improved Oral Delivery of Donepezil Hydrochloride in Alzheimer's Disease Treatment

ABSTRACTThe present study focused on fabricating an efficient excipient for donepezil HCl from karaya gum as the base material. The karaya gum was grafted and crosslinked with N‐isopropyl acrylamide and N,N′‐methylene(bis)acrylamide, respectively, using microwave. The successful fabrication of the resulting hydrogel was confirmed and characterized by FTIR, FESEM, and TGA analyses. Remarkably, the synthesized gel exhibited distinct swelling behavior in different pH mediums ranging from 1.2 to 13. As expected, the gel exhibited an impressive 96% release of donepezil, a widely used hydrophilic drug for treating Alzheimer's disease, in a buffer solution of pH 1.2, within a 48‐h timeframe. Kinetic studies further revealed that drug release from the gel aligns with the Higuchi model. Cytotoxicity studies using Drosophila melanogaster as a model system showed the biocompatible nature of the excipient. This characteristic highlights its potential application as a drug carrier for the oral delivery of Donepezil HCl in treating Alzheimer's disease.

Effects of ginger root extract on cognitive impairment and the Nrf2/GPX4/SLC7A11 signaling pathway in aluminum-exposed rats.

Aluminum exposure has been widely demonstrated to cause cognitive impairment and neuronal damage, which are significant factors in many neurodegenerative diseases. Ginger root extract (GRE) has attracted researchers' attention in recent years due to its antioxidant and neuroprotective properties, as a potential therapeutic intervention to mitigate aluminum-induced neural damage.To evaluate the effects of GRE on cognitive impairment and the expression of Nrf2, GPX4, and SLC7A11 in aluminum (Al)-exposed rats. In this study, a total of 60 male Sprague-Dawley (SD) rats were randomly assigned to 6 groups: Control, Al exposure (Al), Clinical Drug, low-dose GRE (Al + L-GRE), medium-dose GRE (Al + M-GRE), and high-dose GRE (Al + H-GRE). All groups, except Control, received 10mg/ml AlCl₃ in drinking water for three months. Post-exposure treatments included saline for Control and Al groups, 0.5mg/kg donepezil hydrochloride for the Clinical Drug group, and 100, 200, and 400mg/kg GRE for the respective GRE groups. Treatments were administered once daily, five days a week, for a duration of one month. Cognitive and spatial abilities were assessed using the Morris water maze and Y-maze tests. Neuronal damage and mitochondrial structure in the hippocampus were evaluated via Nissl staining and transmission electron microscopy. Serum levels of SOD, GSH, MDA, and Fe²⁺ were measured, and Nrf2/GPX4/SLC7A11 mRNA and protein levels in hippocampal tissues were analyzed using real-time PCR and Western blotting. The Al group demonstrated compromised cognitive function, diminished neuronal integrity, disrupted mitochondrial structure, and an imbalance in serum antioxidant levels compared to the Control group.GRE treatment appeared to have a positive effect on cognitive function, potentially contributing to the maintenance of neuronal integrity, possibly aiding in the preservation of mitochondrial structure, and potentially assisting in the regulation of antioxidant levels. Notably, the Al + M-GRE and Al + H-GRE groups demonstrated encouraging enhancements in escape latency, platform crossings, novel arm entries, and time spent in the novel arm. Additionally, these groups showed elevated levels of SOD and GSH, reduced levels of MDA and Fe²⁺, and increased expression of Nrf2, GPX4, and SLC7A11, suggesting a potential beneficial impact of GRE treatment.GRE mitigated cognitive impairment in Al-exposed rats, likely through the Nrf2/GPX4/SLC7A11 signaling pathway, demonstrating its potential neuroprotective effects.

Implication of Let7b/AhR/ARNT/HMGB1/RAGE cascade in neuroplasticity disturbances induced by glucocorticoids and the promising reversible effect of 3,3 diindolymethane: Bidirectional crosstalk of Aryl hydrocarbon receptors

Implication of Let7b/AhR/ARNT/HMGB1/RAGE cascade in neuroplasticity disturbances induced by glucocorticoids and the promising reversible effect of 3,3 diindolymethane: Bidirectional crosstalk of Aryl hydrocarbon receptors

Effect and mechanism of Donepezil hydrochloride on Alzheimer’s disease

Objective: To explore the effect and mechanism of donepezil hydrochloride on Alzheimer’s disease (AD).Methods: Thirty-six 3-month-old SD rats were selected as the research subjects and randomly divided into a normal control (NC) group and a model group. The model group was given continuous intraperitoneal injection of D-galactose solution (120 mg/kg/d) combined with aluminum trichloride (10 mg/kg/d) by gavage for 60 days. Morris water maze test was conducted to test the learning and memory abilities of the rats, and AD rats were selected. After modeling, AD rats were divided into a normal saline (NS) group and a drug treatment (DT) group. The DT group was given donepezil hydrochloride (1.0 mg/kg) by gavage intervention, and the NC group and the NS group were given equal volumes of physiological saline by gavage. After 4 weeks of intervention, Morris water maze test was conducted to detect the escape latency, the number of platform crossings and residence time in the target quadrant, the rats were euthanized, with serum and hippocampal tissues collected, and hippocampal tissue homogenate (10%) was prepared by using NS. Enzyme linked immunosorbent assay (ELISA) was used to detect the inflammatory and oxidative stress indicators in rat hippocampal tissues and serum, and hematoxylin eosin (HE) staining was used to observe pathological damage in rat hippocampal tissues.Results: Compared with the NC group, the NS group showed a significant increase in escape latency (p < .05), a significant decrease in the number of platform crossings and residence time in the target quadrant (p < .05), and a significant decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum and hippocampal tissues (p < .05). The content of malondialdehyde (MDA) was significantly increased (p < .05), and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly increased (p < .05). Compared with the NS group, the DT group can significantly reduce the escape latency (p < .05), increase the number of platform crossings and residence time in the target quadrant (p < .05), significantly increase the activities of SOD and GSH-Px in serum and hippocampal tissues and reduce the content of MDA (p < .05) and the levels of IL-6 and TNF-α (p < .05). After intervention with donepezil hydrochloride, the number of neurons in the hippocampus were significantly increased.Conclusions: Donepezil hydrochloride can improve the learning and memory abilities of rats, reduce the levels of oxidative stress and inflammation in the brain and serum, and improve pathological damage in the hippocampus.