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OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the rats' behavior and the transforming precursor of brain-derived neurotrophic factor (proBDNF) into mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia-reperfusion (IR), so as to explore its mechanisms underlying improvement of learning and memory ability. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 6 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (1 Hz/20 Hz) was applied to GV24 and GV20 for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria 24 h after modeling and after intervention. Morris water maze test was used to detect the learning and memory function of the rats. TTC staining was used to evaluate the cerebral infarction volume on the affected side. The protein expression levels of proBDNF, mBDNF, tissue plasminogen activator (tPA), tyrosine kinase receptor B (TrkB) and p75 neurotrophin receptor (p75NTR) in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score, the percentage of cerebral infarction volume and the expression levels of proBDNF and p75NTR protein in hippocampus were increased (P<0.01), while the times of crossing the original platform and the total distance in the target quadrant, the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the neurological function score, the percentage of cerebral infarction volume, and the expression levels of proBDNF and p75NTR protein in hippocampus were decreased (P<0.01, P<0.05), while the times of crossing the original platform, the total distance in the target quadrant, and the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were increased (P<0.05, P<0.01) in the EA group. CONCLUSIONS: EA can alleviate learning and memory impairment in IR rats, which may be related to its function in up-regulating the expression of tPA protein and promoting the transformation of proBDNF to mBDNF, thus improving the synaptic plasticity.
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Isquemia Encefálica , Factor Neurotrófico Derivado del Encéfalo , Electroacupuntura , Trastornos de la Memoria , Plasticidad Neuronal , Precursores de Proteínas , Daño por Reperfusión , Animales , Humanos , Masculino , Ratas , Puntos de Acupuntura , Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia , Isquemia Encefálica/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Hipocampo/metabolismo , Aprendizaje , Memoria , Trastornos de la Memoria/terapia , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/etiología , Ratas Sprague-Dawley , Receptor trkB/metabolismo , Receptor trkB/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/terapia , Daño por Reperfusión/genéticaRESUMEN
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.
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Fármacos Neuroprotectores , Escopolamina , Ratones , Animales , Escopolamina/efectos adversos , Fármacos Neuroprotectores/efectos adversos , Peróxido de Hidrógeno/farmacología , Agua/farmacología , Acetilcolinesterasa/metabolismo , Donepezilo/farmacología , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Estrés Oxidativo , Aprendizaje por Laberinto , Extractos Vegetales/efectos adversosRESUMEN
Introduction: Aging is an unavoidable process in the body that is accompanied by impaired tissue homeostasis and various changes. Carvacrol has attracted considerable attention for its wide range of pharmacological activities. Therefore, this study attempted to explore the protective effect of carvacrol in aged rats.Materiel and methods: The aged rats were given carvacrol (15 or 30 mg/kg/day) for 4 weeks. Morris water maze and passive avoidance tests were used to determine the learning and memory abilities of the rats. The hippocampus and cortex samples were taken for biochemical analysis.Results: In comparison to young control rats, aged control rats showed learning and memory deficits. There was improvement in the Morris water navigation test and passive avoidance test performance in the treatment groups versus the aged control group. An increment in malondialdehyde (MDA) and a decrease in total thiol groups in the hippocampus and cortex samples of aged control rats in comparison to the young control group were observed. Carvacrol decreased MDA levels and increased total thiol groups in the hippocampus and cortex samples of aged rats.Conclusion: Carvacrol improved learning and memory in aged rats, probably through its anti-oxidation effects.
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Alzheimer's disease (AD) is a primary neurodegenerative disease. It can be caused by aging and brain trauma and severely affects the abilities of cognition and memory of patients. Therefore, it seriously threatens the mental and physical health of humans worldwide. As a traditional Chinese medicine, ginsenosides have been proven to have a variety of pharmacological activities. Ginsenoside Rh4 (Rh4) is one of the rare ginsenosides with higher pharmacological activity than ordinary ginsenosides, but its effect on alleviating AD and its molecular mechanism have not been studied. Here, we investigated the anti-AD effects of Rh4 and its potential mechanisms using an AD mouse model induced by a combination of AlCl3·6H2O and d-galactose. The results showed that Rh4 could significantly improve the ability of cognizance and reduce neuronal damage in mice. Concurrently, Rh4 attenuates amyloid ß accumulation, increases the density of dendritic spines, and logically inhibits synaptic structural damage as a result of neuronal excessive apoptosis and autophagy. Rh4 can not only inhibit the inflammatory response caused by the overactivation of microglia and astrocytes, reduce the levels of pro-inflammatory factors, increase the level of antioxidant enzymes in serum, and significantly improve the activity of antioxidant enzyme SOD1 in the hippocampus but also inhibit the hyperphosphorylation of tau protein in the hippocampus of mice by regulating the Wnt2b/GSK-3ß/SMAD4 signaling pathway. Together, this study provides a theoretical basis for Rh4 in the treatment of AD and reveals that Rh4 is a potential drug for the treatment of AD.
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Enfermedad de Alzheimer , Ginsenósidos , Enfermedades Neurodegenerativas , Humanos , Animales , Ratones , Péptidos beta-Amiloides/genética , Proteínas tau/genética , Ginsenósidos/farmacología , Glucógeno Sintasa Quinasa 3 beta/genética , Enfermedades Neuroinflamatorias , Antioxidantes , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Transducción de SeñalRESUMEN
OBJECTIVE: To observe the effect of electroacupuncture on brain-derived neurotrophin factor (BDNF) / tyrosine kinase receptor B (TRKB) / cyclic adenosine monophosphate response element binding protein (CREB) pathway, synaptic plasticity marker protein and synaptic ultrastructure in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia reperfusion (IR), so as to explore its mechanisms underlying improvement of cognitive impairment after stroke. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 12 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (2 Hz/10 Hz, 1-3 mA) was applied to "Shenting" (GV24) and "Baihui" (GV20) for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria. Morris water maze test was used to detect the learning and memory function of the rats. Nissl staining was used to observe the pathological morphology of the hippocampus. Transmission electron microscopy was used to observe the ultrastructure of the syna-pse in the hippocampus, the synaptic gap width and postsynaptic dense substance (PSD) thickness were measured. Immunofluorescence staining was used to observe the positive expression levels of BDNF, PSD-95 and synaptophysin (SYN) in hippocampal CA1 region. The protein expression levels of BDNF, TRKB, CREB, PSD-95, and SYN in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score and escape latency (EL) were significantly increased (P<0.01), the times of crossing the original platform were decreased (P<0.01), the number of neurons in the CA1 area of the hippocampus was reduced, with incomplete morphology, widened synaptic gaps and significantly decreased PSD thickness (P<0.01), the positive expressions of BDNF, PSD-95, SYN and the protein expression levels of BDNF, TRKB, CREB, PSD-95, SYN were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function scores and EL on the 12th and 13th day were decreased (P<0.01, P<0.05), the times of crossing the original platform were increased (P<0.01), the morphology of hippocampal CA1 neurons improved, the synaptic gaps was decreased (P<0.01), the PSD thickness was significantly increased (P<0.01), the positive expressions of BDNF, PSD-95, SYN, and the protein expression levels of BDNF, TRKB, CREB, PSD-95, SYN were increased (P<0.05, P<0.01) in the EA group. CONCLUSION: EA can alleviate cognitive impairment in IR rats, which may be related to its function in up-regulating the proteins of BDNF/TRKB/CREB pathway, promoting the expressions of synaptic plasticity marker proteins PSD-95 and SYN, thus improving the synaptic plasticity.
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Electroacupuntura , Daño por Reperfusión , Animales , Ratas , Ratas Sprague-Dawley , Factor Neurotrófico Derivado del Encéfalo/genética , Infarto Cerebral , Hipocampo , Daño por Reperfusión/genética , Daño por Reperfusión/terapia , Plasticidad Neuronal/genética , Región CA1 Hipocampal , Transducción de SeñalRESUMEN
BACKGROUND: The present study aimed to assess whether folic acid (FA) have potential to prevent memory impairment caused by nicotine (Nico) withdrawal in adolescent male rats. METHODS AND MATERIALS: The experiments were divided into 7 groups: 1) vehicle, 2) Nico (Nico 2 mg/kg injection from 21 to 42 days of ages), 3-5) Nico FA5/10/15 mg/kg (received Nico from 21 to 42 days of ages and received FA at three doses 5, 10 and 15 mg/kg 43-63 days of ages), and 6) received normal saline from 21 to 42 days of age after that received FA 15 mg/kg by oral gavage from 43 to 63 days of age. At 64-69 days of ages, behavioral tests related to memory including Morris Water Maze (MWM) and Object Recognition Test (ORT) were performed and related biochemical analysis including the hippocampal levels of oxidative stress markers, inflammatory indices, brain-derived neurotrophic factor (BDNF), nitrite, amyloid-B and acetylcholinesterase [1] were measured. RESULTS: Results showed that nicotine exposure in adolescence followed by withdrawal dramatically impaired learning and memory performance along with affecting a variety of biochemical markers in the hippocampal tissues. In addition, it was observed that administration of FA significantly ameliorated Nico withdrawal-induced adverse effects through restoration of the mentioned biochemical disturbances. CONCLUSION: The present study and other relevant researches demonstrated that FA as a well-known, inexpensive, and safe supplement has strong potential to either prevent or ameliorate the detrimental effect of Nico withdrawal. However, further investigation is required to be more elucidated the precise mechanisms underlying memory impairment-induced by Nico withdrawal.
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BACKGROUND: The primary phytoconstituents reported to have neuroprotective effects are flavonoids and phenolic compounds. Aerva persica roots are reported to be rich in flavonoids and phenolic compounds. Therefore, this study aimed to explore the nootropic potential of Aerva persica roots. OBJECTIVE: The objective of this study was to evaluate the nootropic potential of Aerva persica roots against D-galactose-induced memory impairment. METHODS: In this study, the roots of Aerva persica were extracted with 70% ethanol. The obtained extract was evaluated for total phenolic content using the Folin-Ciocalteu method and total flavonoid content using the aluminium chloride colorimetric assay. Afterward, the acute oral toxicity of the extract was determined following the Organisation for Economic Co-operation and Development (OECD) guideline 423. Additionally, two doses of Aerva persica (100 and 200 mg/kg body weight (BW)) were evaluated for their nootropic potential against D-galactose-induced memory impairment. The nootropic potential of the crude extract was assessed through a behavioural study and brain neurochemical analysis. Behavioural studies involved the evaluation of spatial reference- working memory using the radial arm maze test and the Y-maze test. Neurochemical analysis was performed to determine the brain's acetylcholine, acetylcholinesterase, glutathione (GSH), and malondialdehyde (MDA) levels. RESULTS: The total phenolic content and total flavonoid content were found to be 179.14 ± 2.08 µg GAE/mg and 273.72 ± 3.94 µg QE/mg, respectively. The Aerva persica extract was found to be safe up to 2000 mg/kg BW. Following the safety assessment, the experimental mice received various treatments for 14 days. The behavioural analysis using the radial maze test showed that the extract at both doses significantly improved spatial reference-working memory and reduced the number of total errors compared to disease control groups. Similarly, in the Y-maze test, both doses significantly increased the alteration percentage and the percentage of novel arm entry (both indicative of intact spatial memory) compared to disease control. In neurochemical analysis, Aerva persica at 200 mg/kg significantly normalised the acetylcholine level (p<0.0001) and GSH level (p<0.01) compared to disease control. However, the same effect was not observed with Aerva persica at 100 mg/kg. Additionally, Aerva persica at 200mg/kg BW significantly decreased the acetylcholinesterase level (p<0.0001) and decreased the brain's MDA level (p<0.01) compared to the disease control, whereas the effect of Aerva persica at 100 mg/kg BW in reducing acetylcholinesterase was non-significant. CONCLUSION: Based on the results, it can be concluded that the nootropic potential of Aerva persica was comparable to that of the standard drug, Donepezil, and the effect might be attributed to the higher content of flavonoids and phenolic compounds.
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Amaranthaceae , Nootrópicos , Ratones , Animales , Nootrópicos/farmacología , Galactosa/toxicidad , Acetilcolinesterasa , Acetilcolina/efectos adversos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Glutatión/efectos adversos , Etanol , Flavonoides/farmacología , Flavonoides/uso terapéutico , Aprendizaje por LaberintoRESUMEN
Scopolamine is a well-known pharmacological agent responsible for causing memory impairment in animals, as well as oxidative stress and neuroinflammation inducer which lead to the development of Alzheimer disease. Although a cure for Alzheimer's disease is unavailable. Ranuncoside, a metabolite obtained from a medicinal plant has demonstrated antioxidant and anti-inflammatory properties in vitro, making it a promising treatment with potential anti-Alzheimer disease properties. However, as ranuncoside has not been evaluated for its antioxidant and anti-neuroinflammatory properties in any in vivo model, our study aimed to evaluate its neurotherapeutic efficacy against scopolamine-induced memory impairment in adult male albino mice. Mice were randomly divided into four experimental groups. Mice of group I was injected with saline, group II was injected with scopolamine (1 mg/kg/day) for 3 weeks. After receiving a daily injection of scopolamine for 1 week, the mice of group III were injected with ranuncoside (10 mg/kg) every other day for 2 weeks along with scopolamine daily and group IV were injected with ranuncoside on 5th alternate days. Behavioral tests (i.e., Morris water maze and Y-maze) were performed to determine the memory-enhancing effect of ranuncoside against scopolamine's memory deleterious effect. Western blot analysis was also performed to further elucidate the anti-neuroinflammatory and antioxidant effects of ranuncoside against scopolamine-induced neuroinflammation and oxidative stress. Our results showed memory-enhancing, anti-neuroinflammatory effect, and antioxidant effects of ranuncoside against scopolamine by increasing the expression of the endogenous antioxidant system (i.e., Nrf2 and HO-1), followed by blocking neuroinflammatory markers such as NF-κB, COX-2, and TNF-α. The results also revealed that ranuncoside possesses hypoglycemic and hypolipidemic effects against scopolamine-induced hyperglycemia and hyperlipidemia in mice as well as scopolamine's hyperglycemic effect. In conclusion, our findings suggest that ranuncoside could be a potential agent for the management of Alzheimer's disease, hyperglycemia, and hyperlipidemia.
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Tabernaemontana arborea (Apocynaceae) is a Mexican tree species known to contain ibogan type alkaloids. This study aimed at determining central nervous system-related activities of an alkaloid extract obtained from the root bark of T. arborea. A gas chromatography-mass spectrometry (GC-MS) analysis was performed to describe the alkaloid profile of the extract. A wide dosing range (0.1 to 56.2 mg/kg) of this extract was evaluated in different murine models. Electrical brain activity was examined by electroencephalography (EEG). The extract's effects on motor coordination, ambulatory activity, and memory were analyzed based on the rotarod, open field (OFT), and object recognition tests (ORT), respectively. Antidepressant and antinociceptive activities were determined using the forced swimming test (FST) and the formalin assay, respectively. In order to elucidate the underlying mechanisms of action, the 5-HT1A receptor antagonist WAY100635 (1 mg/kg) or the opioid receptor antagonist naloxone (1 mg/kg) was included in the latter experiments. GC-MS analysis (µg/mg extract) confirmed the presence of the monoterpenoid indole alkaloids (MIAs) voacangine (207.00), ibogaine (106.33), vobasine (72.81), coronaridine (30.72), and ibogamine (24.2) as principal constituents of the extract, which exhibited dose- and receptor-dependent antidepressant (0.1 to 1 mg/kg; 5-HT1A) and antinociceptive (30 and 56.2 mg/kg; opioid) effects, without altering motor coordination, ambulatory activity, and memory. EEG indicated CNS depressant activity at high doses (30 and 56.2 mg/kg). The root bark of T. arborea contains a mixture of alkaloids that may hold therapeutic value in pain relief and the treatment of psychiatric diseases without causing neurotoxic activity at effective doses.
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Antineoplásicos , Alcaloides de Triptamina Secologanina , Tabernaemontana , Animales , Ratones , Tabernaemontana/química , Modelos Animales de Enfermedad , Estructura Molecular , Extractos Vegetales/farmacología , Extractos Vegetales/química , Sistema Nervioso Central , Analgésicos/farmacología , Transmisión SinápticaRESUMEN
In traditional medicine, Tarooneh (a hardcover of the date palm; Phoenix dactylifera) has known as a sedative and relaxant medicine. In this study, we evaluated the protective effects of Tarooneh in the anxiety-like behavior, cognitive deficit, and neuronal damages in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and frontal cortex neurons employing a rat model of chronic restraint stress. The animal received Tarooneh extract for 14 consecutive days in water, and chronic restraint stress was performed daily during this period. The results of the Barnes maze test showed that treatment with Tarooneh significantly improves spatial memory parameters such as latency time to find the target hole, number of errors, and distance traveling compared to the stress group. The EPM results showed that Tarooneh significantly increased the time spent in open arms and the percentage of entries into open arms and significantly decreased the frequency of head dipping behavior compared to animals in the stress group. Golgi-Cox staining indicates that loss of neural spine density in DG, CA1, CA3, and frontal cortex due to chronic restraint stress, was prevented with daily administration of Tarooneh. The results of cresyl-violet staining indicate that Tarooneh significantly increased the number of CV-positive neurons in the frontal cortex and CA1 region of the hippocampus compared to the stress group. Our results suggest that Tarooneh potentially prevented and improved effects in anxiety-like behavior, memory impairment, and synaptic plasticity loss in frontal and hippocampal neurons induced by chronic restraint stress. In conclusion, our results suggest that Tarooneh prevented and improved anxiety-like behavior, cognitive deficit, and neuronal damages in the CA1, CA3, and DG regions of the hippocampus and frontal cortex neurons induced by chronic restraint stress.
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BACKGROUND: Acanthopanax senticosus (AS) is a medicinal and food plant with many physiological functions, especially nerve protection. Its extract has many functional components, including polysaccharides, flavonoids, saponins, and amino acids. Our previous study indicated that AS extract protected against nerve damage caused by radiation. However, little is known about the gut-brain axis mechanism of AS and its impact on radiation-induced learning and memory impairment. METHOD: In 60 Co-γ ray-irradiated mice, we investigated the changes in behavior, neurotransmitters and gut microbiota after different days of administration of AS extract as a dietary supplement. RESULTS: The AS extract improved learning and memory ability in mice, and the neurotransmitter levels in the hippocampus and colon started to change from the 7th day, which accompanied changes of the gut microbiota, a decreased abundance of Helicobacter on the 7th day and an increased abundance of Lactobacillus on the 28th day. Among the marker bacteria, Ruminococcus and Clostridiales were associated with 5-HT synthesis, and Streptococcus were associated with 5-HT and ACH synthesis. In addition, the AS extract increased the tight junction protein, inhibited inflammation levels in colon, and even increased the relative protein expression of BDNF and NF-κB and decreased the relative protein expression of IκBα in the hippocampus of irradiated mice. CONCLUSION: These results will lay the foundation for further study on the mechanism of the gut-brain axis of AS in preventing radiation-induced learning and memory impairment.
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Eleutherococcus , Microbioma Gastrointestinal , Ratones , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Eleutherococcus/química , Serotonina , Neurotransmisores , ComunicaciónRESUMEN
Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.
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Electroacupuntura , Accidente Cerebrovascular Isquémico , Humanos , Aprendizaje , Transducción de Señal/fisiologíaRESUMEN
Alzheimer's disease is a worldwide public health problem. However, the treatment method and treatment effects are limited. The stages of preclinical Alzheimer's disease are thought to be a better intervention period. Thus, in this review, food is given focus and the intervention stage put forward. We summarized the role of diet, nutrient supplementation, and microbioecologics in cognitive decline and found that interventions such as modified Mediterranean-ketogenic diet, nuts, vitamin B, and Bifidobacterium breve A1 are beneficial to cognition protection. Eating, rather than just taking medicine, is suggested to be an effective treatment method for older adults at risk for Alzheimer's disease.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Dieta Mediterránea , Complejo Vitamínico B , Humanos , Anciano , Enfermedad de Alzheimer/prevención & control , Cognición , Disfunción Cognitiva/etiología , Disfunción Cognitiva/prevención & controlRESUMEN
Memory impairment (MI) is caused by a variety of causes, endangering human health. Yuanzhi San (YZS) is a common prescription used for the treatment of MI, but its mechanism of action needs further exploration. The purpose of this study was to investigate this mechanism through lipidomics and network pharmacology. Sprague Dawley (SD) rats were divided randomly into the normal, model, and YZS groups. The rats were gavaged with aluminum chloride (200â mg/kg) and intraperitoneally injected with D-galactose (400â mg/kg) every day for 60â days, except for the normal group. From the 30th day, YZS (13.34â g/kg) was gavaged once a day to the rats in the YZS group. Post-YZS treatment, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC/MS) analysis was implemented to conduct a lipidomics study in the hippocampus of rats with memory impairment induced by aluminum chloride and D-galactose. Eight differential metabolites were identified between the normal group and the model group, whereas between the model group and the YZS group, 20 differential metabolites were established. Metabolic pathway analysis was performed on the aforementioned lipid metabolites, all of which were involved in sphingolipid and glycerophospholipid metabolism. Furthermore, serum pharmacochemistry analysis of YZS was carried out at the early stage of our research, which discovered 62 YZS prototype components. The results of the network pharmacology analysis showed that they were related to 1030 genes, and 451 disease genes were related to MI. There were 73 intersections between the YZS and MI targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these targets were closely related to the sphingolipid metabolic, calcium signaling, and other pathways. The integrated approach of lipidomics and network pharmacology was then focused on four major targets, including PHK2, GBA, SPTLC1, and AChE, as well as their essential metabolites (glucosylceramide, N-acylsphingosine, phosphatidylserine, phosphatidylcholine, and phosphatidylcholine) and pathways (sphingolipid, glycerophospholipid, and arachidonic acid metabolism). The significant affinity of the primary target for YZS was confirmed by molecular docking. The obtained results revealed that the combination of lipidomics and network pharmacology could be used to determine the effect of YZS on the MI biological network and metabolic state, and evaluate the drug efficacy of YZS and its related mechanisms of action.
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Medicamentos Herbarios Chinos , Lipidómica , Farmacología en Red , Animales , Humanos , Ratas , Cloruro de Aluminio , Medicamentos Herbarios Chinos/farmacología , Galactosa , Glicerofosfolípidos , Lipidómica/métodos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Farmacología en Red/métodos , Fosfatidilcolinas , Ratas Sprague-DawleyRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by ß-amyloid (Aß) plaques, neurofibrillary tangles, neuronal cell loss, and oxidative stress. Further deposition of Aß in the brain induces oxidative stress, neuroinflammation, and memory dysfunction. Hawthorn (Crataegus pinnatifida Bge.) leaf, a known traditional Chinese medicine, is commonly used for the treatment of hyperlipidemia, heart palpitations, forgetfulness, and tinnitus, and its main bioactive components are Hawthorn Leaf Flavonoids (HLF). In this study, we investigated the neuroprotective effects of the HLF on the Aß25-35 (bilateral hippocampus injection) rat model of AD. The results showed that the oral administration of HLF at a dose of 50, 100, and 200 mg/kg for 30 days significantly ameliorated neuronal cell damage and memory deficits, and markedly increased the enzyme activities of superoxide dismutase and catalase, and the content of glutathione whereas it decreased the malondialdehyde content in the Aß25-35 rat model of AD as well as suppressed the activation of astrocytes. In addition, HLF up-regulated Nrf-2, NQO-1, and HO-1 protein expressions. Also, it reduced neuroinflammation by inhibiting activation of astrocytes. In summary, these results indicated that HLF decreased the oxidative stress via activating Nrf-2/antioxidant response element signaling pathways, and may suggest as a potential candidate for AD therapeutic agent.
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Enfermedad de Alzheimer , Crataegus , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Ratas , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Flavonoides/farmacología , Fármacos Neuroprotectores/uso terapéutico , Enfermedades Neuroinflamatorias , Enfermedades Neurodegenerativas/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Hojas de la PlantaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendrum viscosum is an important medicinal plant in Ayurveda in Bangladesh and its leaves are used as a remedy for various diseases such as anti-inflammatory, antibacterial, hyperglycemic, hepatoprotective effects. AIM OF THE STUDY: The present study aimed to evaluate the protective effect of aqueous extract of C. viscosum leaves against Pb-induced neurobehavioral and biochemical changes in mice. MATERIALS AND METHODS: Swiss albino mice were divided as a) control, b) lead treated (Pb) and c) C. viscosum leaves (Cle) d) Pb plus Cle groups. Pb-acetate (10 mg/kg body weight) was given to Pb and Pb + Cle groups mice, and water extract of leaves (50 mg/kg body weight) was provided as supplementation to Cle and Pb + Cle groups mice for 30 days. Elevated plus maze and Morris water maze tests were used for evaluating anxiety, spatial memory and learning, respectively. Status of cholinesterase, SOD, GSH enzyme activity and neurotoxicity markers such BDNF and Nrf2 levels were analyzed in the brain tissue of experimental mice. RESULTS: Poorer learning, inferior spatial memory, and increased anxiety-like behavior in Pb-exposure mice were noted when compared to control mice in Morris water maze and elevated plus maze test, respectively. In addition, expression of BDNF and Nrf2, cholinesterase activity along with antioxidant activity were significantly reduced compared to control group (p < 0.01). Interestingly, C. viscosum leaves' aqueous extract supplementation in Pb-exposed mice provide a significant improved neurochemical and antioxidant properties through the augmentation of activity of cholinergic enzymes, and upregulation of BDNF and Nrf2 levels in the brain tissue compared to Pb-exposed mice. CONCLUSIONS: This study suggested that C. viscosum leaves restore the cognitive dysfunction and reduce anxiety-like behavior through upregulation of BDNF mediated Akt-Nrf2 pathway in Pb-exposure mice.
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Clerodendrum , Proteínas Proto-Oncogénicas c-akt , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Regulación hacia Arriba , Plomo/toxicidad , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Memoria Espacial , Colinesterasas , Peso Corporal , Aprendizaje por LaberintoRESUMEN
Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3ß (p-GSK3ß) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3ß and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.
Asunto(s)
Humulus , Sobrecarga de Hierro , Ratas , Femenino , Ratones , Animales , Humulus/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Estrés Oxidativo , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Sobrecarga de Hierro/inducido químicamente , Sobrecarga de Hierro/tratamiento farmacológico , Hierro/farmacología , Hemo-Oxigenasa 1/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/farmacologíaRESUMEN
AIM OF THE STUDY: The study aimed at evaluating the potentials of stem bark extracts of Bombax costatum (B. costatum) on seizure, pentylenetetrazole (PTZ) induced kindling and associated changes in wistar albino rats. MATERIALS AND METHODS: Phase 1 evaluated which extract of B. costatum (chloroform, ethanol and n-hexane) is most effective in preventing seizure in acute PTZ-induced (85mg/kg) seizure in rats. Phase 2 evaluated the potentials of stem bark chloroform extract of B. costatum in PTZ-kindled rats at a dose 250 and 500mg/kg in comparison to diazepam. As its effects on memory, oxidative stress markers, neurotransmitters and brain histology were evaluated. Phase 3 determined the probable curative effects of B. costatum on fully kindled rats. RESULTS: In phase 1, Chloroform extract of B. coststum 500mg/kg is the most effective (P<0.05) in preventing seizure as compared to ethanol and n-hexane extracts. In phase 2, chloroform extract of B. costatum delayed the development of kindling, improved kindling associated cognitive impairment and alterations of glutamate and gamma-aminobutyric acid (GABA). Further, it attenuated oxidative stress besides the maintenance of neuronal architecture of the hippocampus. CONCLUSION: Conclusively, chloroform stem bark extract of B. costatum antagonizes PTZ-induced seizure progression, protects against kindling induced cognitive impairment and oxidative stress. Additionally, it also increases the brain level of GABA at high dose and prevented against kindling-induced hippocampal disruptions. Hence, this justifies its use traditionally in the treatment of epileptic seizures.
Asunto(s)
Bombax , Fármacos Neuroprotectores , Ratas , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Cloroformo/efectos adversos , Ácido gamma-Aminobutírico/efectos adversos , Fármacos Neuroprotectores/efectos adversos , Pentilenotetrazol/efectos adversos , Corteza de la Planta , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , AnimalesRESUMEN
Alcohol-induced aggression and related violence is a serious and common social problem globally. Alcohol use is increasingly found in the form of alcoholic herbal mixtures (AHM) with indiscriminate and unregulated alcohol content. This study investigated the effects of AHM on aggressive-like, neurocognitive impairment and brain biochemical alteration in mice. Thirty-two male resident mice were paired housed with female mice for 21 days in four groups (n = 8). Resident mice were treated orally with normal saline, AHM, ethanol and AHM + ethanol daily for 14 days. Aggressive-like behaviour was scored based on the latency and frequency of attacks by the resident mouse on the intruder. Neurocognitive impairment was determined using the Y-maze test (YMT) and novel object recognition test (NORT). Acetylcholinesterase, glutamic acid decarboxylase (GAD), pro-inflammatory and oxidative stress parameters were determined in the prefrontal cortex (PFC). Neuronal morphology, cytochrome c (Cyt-c) and nuclear factor-kappa B (NF-ĸB) expressions were determined. AHM and in combination with ethanol showed an increased index of aggression typified by frequency of attack and reduced latency to attack when compared to normal saline-treated animals. Co-administration of AHM and ethanol significantly reduced cognitive correct alternation (%) and discrimination index in the YMT and NORT, respectively. AHM and ethanol increased acetylcholinesterase, Pro-inflammatory cytokines and oxidative stress parameters while they reduced GAD. There were significantly reduced neuronal counts and increased expression of Cyt-c and NF-ĸB, respectively Alcoholic herbal mixture increased aggressiveness and caused neurocognitive impairment via increased oxido-inflammatory stress in the prefrontal cortex.
Asunto(s)
Acetilcolinesterasa , FN-kappa B , Ratones , Masculino , Femenino , Animales , Acetilcolinesterasa/metabolismo , FN-kappa B/metabolismo , Enfermedades Neuroinflamatorias , Solución Salina/metabolismo , Solución Salina/farmacología , Etanol/toxicidad , Corteza Prefrontal/metabolismo , Agresión , ApoptosisRESUMEN
Fluoride pollution is widely present in the living environment. As a critical period of brain development, the perinatal period is extremely vulnerable to fluoride. Studies have found that choline can protect the brain's memory and enhance the ability to focus. However, the effect of choline on perinatal fluoride-induced nerve damage remains unclear. Therefore, 32 Kunming newly conceived female mice and their offspring mice were randomly divided into control, NaF, LC + NaF, and HC + NaF groups, and the HE staining, Y-maze test, RT-PCR, western blotting, immunohistochemistry, etc. were used in this study. The results showed that fluoride decreased the brain organ coefficients and brain protein content (p < 0.05, p < 0.01), and caused histomorphological damage in the hippocampus and cortex, which suggested that fluoride affected the development of the brain and damaged the brain. Moreover, the results of the Y-maze test showed that fluoride increased the number of learning days, error reaction time, and total reaction time, and decreased the AchE activity in the brain (p < 0.05, p < 0.01), which indicated that fluoride reduced the learning and memory ability of the mice. Besides, the results showed that fluoride decreased the mRNA and protein expression levels of α4ß2 nAChRs and α7 nAChRs in the hippocampus and cortex (p < 0.05, p < 0.01). However, perinatal choline supplementation reversed the aforementioned fluoride-induced changes. In short, these results demonstrated that choline alleviated perinatal fluoride-induced learning and memory impairment, which will provide a rationale for the mitigation and prevention of fluoride-induced brain damage.