RESUMO
Alzheimer's disease (AD) is a neurodegenerative disease. Ginsenoside Rg2 has shown potential in treating AD, but the underlying protein regulatory mechanisms associated with ginsenoside Rg2 treatment for AD remain unclear. This study utilized scopolamine to induce memory impairment in mice, and proteomics methods were employed to investigate the potential molecular mechanism of ginsenoside Rg2 in treating AD model mice. The Morris water maze, hematoxylin and eosin staining, and Nissl staining results indicated that ginsenoside Rg2 enhanced cognitive ability and decreased neuronal damage in AD mice. Proteomics, western blot, and immunofluorescence results showed that ginsenoside Rg2 primarily improved AD mice by downregulating the expression of LGMN, LAMP1, and PSAP proteins through the regulation of the lysosomal pathway. Transmission electron microscopy and network pharmacology prediction results showed a potential connection between the mechanism of ginsenoside Rg2 treatment for AD mice and lysosomes. The comprehensive results indicated that ginsenoside Rg2 may improve AD by downregulating LGMN, LAMP1, and PSAP through the regulation of the lysosomal pathway.
Assuntos
Ginsenosídeos , Lisossomos , Transtornos da Memória , Proteômica , Escopolamina , Animais , Ginsenosídeos/farmacologia , Ginsenosídeos/administração & dosagem , Camundongos , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Escopolamina/efeitos adversos , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Transtornos da Memória/induzido quimicamente , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Proteína 1 de Membrana Associada ao LisossomoRESUMO
Flammulina velutipes protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from F. velutipes protein hydrolysates in vitro and validate the protective effects of YVYAETY on memory impairment in scopolamine-induced mice. The F. velutipes protein was hydrolyzed by simulated gastrointestinal digestion, followed by purification through ultrafiltration and gel chromatography. The fraction exhibiting the strongest neuroprotective activity was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main identified peptides (SDLKPADF, WNDHYY, YVYAETY, and WFHPLF) effectively mitigated excessive ROS production by increasing SOD and GSH-px activities while inhibiting cell apoptosis and mitochondrial membrane potential (MMP) collapse against oxidative stress in Aß25-35-induced HT22 cells. By molecular docking, the interaction between peptides and the active site of the Keap1-Kelch domain reveals their capacity to regulate the Keap1/Nrf2/HO-1 pathway. In vitro, the peptide YVYAETY had the best effect and can be further validated in vivo. The behavioral tests showed that YVYAETY improved scopolamine-induced cognitive impairment in mice. YVYAETY also alleviated neuron damage including neuron vacuolation and pyknotic nuclei in the hippocampus. Furthermore, it significantly inhibited oxidative stress and suppressed the activation of the Nrf2 pathway. Therefore, this study revealed that YVYAETY had the potential to serve as a novel neuroprotective agent.
Assuntos
Disfunção Cognitiva , Flammulina , Fármacos Neuroprotetores , Hidrolisados de Proteína , Escopolamina , Animais , Camundongos , Escopolamina/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/química , Flammulina/química , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Simulação de Acoplamento Molecular , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Apoptose/efeitos dos fármacosRESUMO
OBJECTIVE: Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins. RESULTS: When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin. CONCLUSIONS: This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.
Assuntos
Benzopiranos , Fator Neurotrófico Derivado do Encéfalo , Escopolamina , Animais , Ratos , Acetilcolinesterase/metabolismo , Benzopiranos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/metabolismo , Hipocampo/metabolismo , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Estresse Oxidativo , Escopolamina/efeitos adversosRESUMO
Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.
Assuntos
Disfunção Cognitiva , Demência , Sideritis , Ratos , Masculino , Animais , Escopolamina/efeitos adversos , Ratos Wistar , Acetilcolinesterase , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Demência/induzido quimicamente , Demência/tratamento farmacológico , Aprendizagem em LabirintoRESUMO
SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.
Assuntos
Doença de Alzheimer , Juglans , Ratos , Animais , Juglans/química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Escopolamina/efeitos adversos , Simulação de Acoplamento Molecular , Extratos Vegetais/químicaRESUMO
Alzheimer's disease (AD) is one of the major devastating neurodegenerative disorders associated with the gradual decline of an individual's memory, cognition, and ability to carry out day-to-day activities. In the present study, the neuroprotective ability of α-bisabolol ß-d-fucopyranoside (ABFP) was assessed via measurement of antioxidant parameters like lipid peroxidation, glutathione peroxidation, glutathione, protein carbonyl content assays, and caspase-3 activity estimation. Moreover, the acute toxicity of ABFP was estimated in the zebrafish larval model. The results showed that ABFP exhibits little to no toxicity at lower concentrations in the acute toxicity test. ABFP-pretreated and scopolamine-exposed fish exhibited more exploratory behavior in the behavior assay than scopolamine-only induced groups. Additionally, the results of antioxidant enzyme assays revealed reduced oxidative stress and damage in ABFP-treated fish, while enzyme activity experiments carried out with brain homogenate from ABFP-treated fish showed decreased acetylcholinesterase enzyme activity. Overall, it can be concluded that ABFP has the potential to be a promising agent for the treatment of AD in the future.
Assuntos
Doença de Alzheimer , Sesquiterpenos Monocíclicos , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Escopolamina/efeitos adversos , Antioxidantes/metabolismo , Acetilcolinesterase/metabolismo , Carbonilação Proteica , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo , Doença de Alzheimer/induzido quimicamente , Glutationa/metabolismoRESUMO
Experiments have demonstrated that frankincense may offer protection against scopolamine-induced Alzheimer's disease by mitigating cholinergic dysfunction and inhibiting inflammatory mediators. Nevertheless, its instability and limited water solubility lead to diminished medicinal efficacy. In this study, we utilized PMBN (poly [MPC-co-(BMA)-co-(MEONP)]) as a nanocarrier for targeted brain drug delivery of frankincense, employing lactoferrin as a ligand for precise targeting. Characterization of nanoparticle properties was conducted through FTIR and FESEM analysis, and the in-vitro drug release percentage from the nanoparticles was quantified. To induce Alzheimer's-like dementia in rats, scopolamine was intraperitoneally administered at a dose of 1 mg/kg/day for 14 days. Subsequently, behavioral assessments (Y-maze, passive avoidance test, tail suspension test) were performed, followed by evaluations of acetylcholinesterase (AChE), reduced glutathione (GSH), catalase (CAT), and brain histopathology at the conclusion of the treatment period. The results revealed that the nanoparticles had a size of 106.6 nm and a zeta potential of -3.8 mV. The maximum release of frankincense in the PBS environment from PMBN nanoparticles was 18.2 %, in accordance with the Peppas model. Behavioral tests indicated that targeted drug nanoparticles (F-PMBN-Lf) exhibited the capability to alleviate stress and depression while enhancing short-term memory in scopolamine-induced animals. Additionally, F-PMBN-Lf counteracted the scopolamine-induced elevation of AChE activity and GSH levels. However, it resulted in decreased activity of the antioxidant enzyme CAT compared to the scopolamine group. Histological analysis of brain tissue suggested that F-PMBN-Lf exerted a notable neuroprotective effect, preserving neuronal cells in contrast to the scopolamine-induced group. It appears that the polymer nanoparticles containing this plant extract have introduced a novel neuroprotective approach for the treatment of Alzheimer's disease.
Assuntos
Doença de Alzheimer , Franquincenso , Animais , Ratos , Acetilcolinesterase/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Franquincenso/farmacologia , Franquincenso/uso terapêutico , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Aprendizagem em Labirinto , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo , Escopolamina/efeitos adversos , Escopolamina/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas/uso terapêuticoRESUMO
Dry eye disease is a common condition in patients of all ages, causing discomfort and potential visual problems. Current treatments, including artificial tears and anti-inflammatory drugs, have certain limitations, encouraging research into alternative therapies. We investigated the therapeutic potential of multi-wavelength light-emitting diode (LED) irradiation of mice with dry eye. First, we showed that multi-wavelength LED irradiation was non-toxic to human corneal epithelial cells and improved cell viability. We then used a scopolamine-induced mouse model of dry eye to assess the effects of multi-wavelength LED irradiation on various clinical parameters. This treatment increased the tear volume and reduced corneal irregularity, thus improving dry eye. Histological analysis revealed that multi-wavelength LED irradiation protected against corneal epithelial damage and the associated reduction in epithelial thickness and would thus improve the corneal health of dry eye patients. Multi-wavelength LED irradiation significantly reduced the corneal levels of pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α; the treatment was thus anti-inflammatory. Our results suggest that multi-wavelength LED irradiation may serve as a safe and effective treatment for dry eye, alleviating symptoms, reducing inflammation, and promoting corneal health.
Assuntos
Lesões da Córnea , Síndromes do Olho Seco , Humanos , Camundongos , Animais , Escopolamina/efeitos adversos , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/patologia , Lágrimas , Córnea/patologia , Modelos Animais de Doenças , Anti-Inflamatórios/efeitos adversos , Lesões da Córnea/patologiaRESUMO
The oil of Torreya grandis (TGO), a common nut in China, is considered to be a bioactive edible oil and has a great value in functional food development. In this study, the neuroprotective effects of TGO were investigated on a scopolamine (SCOP)-induced C57BL/6J mouse model. The mice were pretreated with TGO for 30 days (1000 mg per kg per day and 3000 mg per kg per day, i.g.). Behavioral tests showed that the supplementation of TGO could prevent the cognitive deficits induced by SCOP. TGO rebalanced the disorder of the cholinergic system by upgrading the level of acetylcholine. TGO also alleviated the over-activation of microglia and inhibited neuroinflammation and oxidative stress. Additionally, TGO could regulate the composition of gut microbiota, increase the production of short-chain fatty acids, and decrease the content of lipopolysaccharides in the serum. In conclusion, TGO has the potential to prevent loss of memory and impairment of cognition, which may be related to its regulation of the gut microbiota-metabolite-brain axis.
Assuntos
Disfunção Cognitiva , Taxaceae , Camundongos , Animais , Escopolamina/efeitos adversos , Camundongos Endogâmicos C57BL , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Estresse OxidativoRESUMO
This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aß(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aß(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.
Assuntos
Fármacos Neuroprotetores , Escopolamina , Camundongos , Animais , Escopolamina/efeitos adversos , Fármacos Neuroprotetores/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Água/farmacologia , Acetilcolinesterase/metabolismo , Donepezila/farmacologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo , Aprendizagem em Labirinto , Extratos Vegetais/efeitos adversosRESUMO
Walnut Oil (WO) is recognized for its potential to improve cognition, but the mechanisms of its action related to improving cognitive impairment are not yet clear. In this study, the components of walnut oil were measured, and it was found that WO supplementation for 8 weeks could significantly prevent cognitive behavioral deficits and synaptic dysfunction induced by intraperitoneal injection of scopolamine (SCOP) in mice. By comparing and analyzing the changes in the hippocampal synaptic structure, oxidative stress, neurotransmitter fluctuations, brain transcriptome, inflammatory factors and gut microbiota in mice from different treatment groups, we observed a significant correlation between synaptic transmission genes, gut microbiota and neurotransmission in the WO supplemented group. It was found that WO supplementation could influence the secretion of neurotransmitters Ach and 5-HT by modulating the gut microbiota in vivo, thereby improving cognitive impairment through the central nervous system and hypothalamic-pituitary-adrenal (HPA) axis regulation.
Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Juglans , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , Escopolamina/efeitos adversos , Encéfalo/fisiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ's neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular trajectories remain ambiguous. Thus, the objective of the current investigation was to examine the potential beneficial effects and underlying mechanisms of TQ in scopolamine (SCOP)-induced neuronal injury to mimic AD in vivo model. METHODS: Thirty mice were divided into normal, SCOP, and TQ groups. The Y-maze and pole climbing tests were performed to measure memory and motor performance. Afterwards, histopathological and immunohistochemical examinations were carried out. Furthermore, peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway-related proteins and genes were detected with an emphasis on the role of miR-9. RESULTS: TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes, histopathological changes, modulation of the expression pattern of PPAR-γ downstream targets with a significant decrease in the deposition of amyloid beta (Aß). CONCLUSIONS: TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity. Consequently, TQ may possess a potential beneficial role against AD development.
Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Animais , Camundongos , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Peptídeos beta-Amiloides , PPAR gama/genética , Escopolamina/efeitos adversosRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder associated with a decline in memory deficits and neuropathological diagnosis with loss of cholinergic neurons in the brains of older adults. Based on these facts and an increasing number of involved people worldwide, this investigation aimed to study the improvement of memory and cognitive impairments via an anticholinergic approach of thiazolidine-2,4-diones (TZDs) in the scopolamine-induced model of Alzheimer type in adult male Wistar rats (n = 40). The results indicated data analysis obtained from in vivo and in vitro tests for (E)-5-(3-hydroxybenzylidene)-3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione (TZ3O) (2 and 4 mg/kg) with the meta-hydroxy group and (E)-5-(4-methoxybenzylidene)-3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione (TZ4M) (2 and 3 mg/kg) with the para-methoxy group showed a neuroprotective effect. TZ3O and TZ4M alleviated the scopolamine-induced cognitive decline of the Alzheimer model in adult male Wistar rats. These initial and noteworthy results could be assumed as a starting point for the evolution of new anti-Alzheimer agents.
Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Ratos , Animais , Masculino , Escopolamina/efeitos adversos , Ratos Wistar , Fármacos Neuroprotetores/farmacologia , Tiazolidinas/efeitos adversos , Transtornos da Memória/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Aprendizagem em Labirinto , Acetilcolinesterase/farmacologiaRESUMO
Overview of: Medicines and Healthcare products Regulatory Agency. Hyoscine hydrobromide patches (Scopoderm 1.5mg Patch or Scopoderm TTS Patch): risk of anticholinergic side effects, including hyperthermia. Drug Safety Update 2023;16:1.
Assuntos
Antagonistas Colinérgicos , Escopolamina , Humanos , Escopolamina/efeitos adversos , Antagonistas Colinérgicos/efeitos adversos , Antagonistas Muscarínicos/efeitos adversosRESUMO
BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD. METHODS: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively. RESULTS: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner. CONCLUSION: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.
Assuntos
Doença de Alzheimer , Venenos de Abelha , Nootrópicos , Ratos , Animais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Nootrópicos/uso terapêutico , Venenos de Abelha/efeitos adversos , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Escopolamina/efeitos adversos , Hipocampo/metabolismo , Aprendizagem em Labirinto , Neurogênese , Modelos Animais de DoençasRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7-8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD.
Assuntos
Doença de Alzheimer , Escopolamina , Ratos , Masculino , Animais , Escopolamina/efeitos adversos , Escopolamina/metabolismo , Acetilcolinesterase/metabolismo , Ratos Sprague-Dawley , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Plasticidade Neuronal , Hipocampo/metabolismo , Doença de Alzheimer/metabolismoRESUMO
OBJECTIVE: The purpose of the study is to assess the bioavailability and neuroprotective effect of hesperetin (Hesp)-loaded nanofibers. METHODS: Electrospinning was used to create and characterize polyvinyl pyrrolidone-based Hesp-loaded nanofibers. To evaluate the produced nanofibers, preclinical studies were conducted. The study involved five groups of Wistar rats, and the treatments were administered as follows. Group 1 (control) was given regular saline for 14 d. On the 14th day, Group 2 was given scopolamine. Group 3 was given donepezil for 14 d and then scopolamine on the 14th. Group 4 was given Hesp for 14 d and then scopolamine on the 14th. Group 5 was given Hesp-loaded nanofibers for 14 d, followed by scopolamine on the 14th. On the 14th day, rats' memory was tested using Cook's pole climbing apparatus and the Morris water maze (MWM). On the 15th day, rats from each group were slaughtered, brain tissues were separated, and biochemical and histological analyses were performed. In addition, in vitro dissolution experiments and pharmacokinetic studies were carried out. RESULTS: When compared to the control group, scopolamine-treated rats had considerably longer escape latency times, as well as increased acetylcholinesterase (AChE) activity, lipid peroxidation, degeneration, and inflammation in the hippocampus. These parameters were greatly recovered by donepezil and Hesp-loaded nanofibers that had been pretreated. Because of the greatly improved bioavailability of Hesp, the Hesp-loaded nanofibers significantly protected rats from scopolamine-induced amnesia. CONCLUSIONS: Hesp-loaded nanofibers have an excellent neuroprotective effect against scopolamine-induced amnesia due to enhanced bioavailability.
Assuntos
Nanofibras , Fármacos Neuroprotetores , Ratos , Animais , Donepezila/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos Wistar , Acetilcolinesterase/metabolismo , Acetilcolinesterase/farmacologia , Acetilcolinesterase/uso terapêutico , Disponibilidade Biológica , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Escopolamina/efeitos adversos , Aprendizagem em LabirintoRESUMO
The loss and progressive dysfunction of neurons are hallmarks of neurodegenerative diseases. The aim of the current study is to explore the effects of photobiomodulation at 460-660 nm (100-1000 lux units) on the progression of scopolamine-induced cognitive dysfunctions in Wistar male rats. Photobiomodulation (PBM) is defined as "the use of monochromatic or quasi-monochromatic light from a low-power laser or light-emitting diode (LED) source to modify or modulate biological functions." Neuroprotective activity was assessed by in vivo models such as the Morris water maze, the elevated plus maze (EPM), and the T-maze. After using scopolamine (1 mg/kg/day) as a dementia induction model for 21 days, the induction was primarily due to impairments in cholinergic transmission, oxidative stress, and inflammation. The in vitro determinations, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1ß), and alkaline phosphatase (ALP), were assessed biochemicals and biomarkers. The structural and morphological integrity of the cortex and hippocampus was investigated through histopathology. In vivo studies of exteroceptive behavior models such as the Morris water maze, the EPM, and the T-maze revealed that administration of scopolamine resulted in enhanced escape latency time (ELT), transfer latency (TL), and decreased percentage alternation, respectively. The levels of AChE, BChE, reduced, GSH, SOD, TNF-α, IL-1ß and ALP were increased, while MDA level was decreased. In contrast to normal and control groups with treatment groups, histopathology of the cortex and hippocampus examination revealed the maintenance of structural integrity and densities of CA1 and CA3 neuronal cells. However, network pharmacology predicted Ca+2 modulation of various pathways, among the treatments with red LED light showed highly significant amelioration compared with normal and control groups. Photobiomodulation by hormesis, chromophores in cells, and tissues excitation can influence neuroprotective effect mainly by scavenging of ROS, variation in the level of GSH MDA and SOD mitochondrial electron transfer, the improved abscopal effects on improved in gut microbiome by resembles the of fecal ALP level correlation of intestinal microbiome, cholinergic neurotransmissions, anti-inflammatory, and antioxidant activities.
Assuntos
Doenças Neurodegenerativas , Fármacos Neuroprotetores , Ratos , Masculino , Animais , Escopolamina/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase/metabolismo , Acetilcolinesterase/farmacologia , Acetilcolinesterase/uso terapêutico , Hormese , Butirilcolinesterase/metabolismo , Butirilcolinesterase/farmacologia , Butirilcolinesterase/uso terapêutico , Fator de Necrose Tumoral alfa/farmacologia , Ratos Wistar , Aprendizagem em Labirinto , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Estresse Oxidativo , Colinérgicos/metabolismo , Colinérgicos/farmacologia , Colinérgicos/uso terapêutico , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Superóxido Dismutase/uso terapêutico , Hipocampo/metabolismoRESUMO
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.
Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Nootrópicos , Óleos Voláteis , Rosmarinus , Ratos , Animais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Escopolamina/efeitos adversos , Mentha piperita , Rosmarinus/química , Nootrópicos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Memória Espacial , Suplementos Nutricionais , HipocampoRESUMO
Aster koraiensis Nakai (AK) leaf reportedly ameliorates health problems, such as diabetes. However, the effects of AK on cognitive dysfunction or memory impairment remain unclear. This study investigated whether AK leaf extract could attenuate cognitive impairment. We found that AK extract reduced the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, phosphorylated-tau (p-tau), and the expression of inflammatory proteins in lipopolysaccharide- or amyloid-ß-treated cells. AK extract exhibited inhibitory activity of control specific binding on N-methyl-D-aspartate (NMDA) receptors. Scopolamine-induced AD models were used chronically in rats and acutely in mice. Relative to negative controls (NC), hippocampal choline acetyltransferase (ChAT) and B-cell lymphoma 2 (Bcl2) activity was increased in rats chronically treated with scopolamine and fed an AK extract-containing diet. In the Y-maze test, spontaneous alterations were increased in the AK extract-fed groups compared to NC. Rats administered AK extract showed increased escape latency in the passive avoidance test. In the hippocampus of rats fed a high-AK extract diet (AKH), the expression of neuroactive ligand-receptor interaction-related genes, including Npy2r, Htr2c, and Rxfp1, was significantly altered. In the Morris water maze assay of mice acutely treated with scopolamine, the swimming times in the target quadrant of AK extract-treated groups increased significantly to the levels of the Donepezil and normal groups. We used Tg6799 Aß-overexpressing 5XFAD transgenic mice to investigate Aß accumulation in animals. In the AD model using 5XFAD, the administration of AK extract decreased amyloid-ß (Aß) accumulation and increased the number of NeuN antibody-reactive cells in the subiculum relative to the control group. In conclusion, AK extract ameliorated memory dysfunction by modulating ChAT activity and Bcl2-related anti-apoptotic pathways, affecting the expression of neuroactive ligand-receptor interaction-related genes and inhibiting Aß accumulation. Therefore, AK extract could be a functional material improving cognition and memory.