Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.569
Filtrar
1.
Life Sci ; 240: 117072, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31751584

RESUMO

Deficits in cognitive functions are often observed in epileptic patients, particularly in temporal lobe epilepsy (TLE). Evidence suggests that this cognitive decline can be associated with the occurrence of focal brain lesions, especially on hippocampus and cortex regions. We previously demonstrated that the erythrinian alkaloids, (+)-erythravine and (+)-11α-hydroxy-erythravine, inhibit seizures evoked in rats by different chemoconvulsants. AIMS: The current study evaluated if these alkaloids would be acting in a neuroprotective way, reducing hippocampal sclerosis, and consequently, improving learning/memory performance. MAIN METHODS: Here we confirmed the anticonvulsant effect of both alkaloids by means of the pilocarpine seizure-induced model and also showed that they enhanced spatial learning of rats submitted to the Morris Water Maze test reverting the cognition deficit. Additionally, immunohistochemistry assays showed that neuronal death and glial activation were prevented by the alkaloids in the hippocampus CA1, CA3 and dentate gyrus regions at both hemispheres indistinctly 15 days after status epilepticus induction. KEY FINDINGS: Our results show, for the first-time, the improvement on memory/learning elicited by these erythrinian alkaloids. Furthermore, data presented herein explain, at least partially, the cellular mechanism of action of these alkaloids. Together, (+)-erythravine and (+)-11α-hydroxy-erythravine seem to be a promising protective strategy against TLE, comprising three main aspects: neuroprotection, control of epileptic seizures and cognitive improvement. SIGNIFICANCE: Moreover, our findings on neuroprotection corroborate the view that seizure frequency and severity, hippocampal lesions and memory deficits are interconnected events.


Assuntos
Alcaloides/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/psicologia , Fármacos Neuroprotetores/uso terapêutico , Transtorno de Aprendizagem Específico/tratamento farmacológico , Transtorno de Aprendizagem Específico/psicologia , Animais , Convulsivantes , Epilepsia/induzido quimicamente , Hipocampo/patologia , Imuno-Histoquímica , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Pilocarpina , Ratos , Ratos Wistar , Esclerose/prevenção & controle , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/psicologia
2.
J Agric Food Chem ; 68(3): 751-758, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31861959

RESUMO

The present study aimed to investigate the combined effects of defatted walnut meal hydrolysate (DWMH) and tea polyphenols (TP) on learning improvement and to explain mechanistically why the combined treatments were more effective than either subject alone. In the step-down avoidance test and the Morris water maze test, codelivery of DWMH and TP was more effective than either individual supplement in reversing memory impairment in scopolamine-treated mice. Mixing with TP significantly facilitated the protective effects of DWMH or DWMH-derived peptides (cationic peptide P1 and anionic peptide P2) on H2O2-injured SH-SY5Y cells. Although combination treatment with TP and DWMH did not significantly alter systemic exposure to P1 or P2 in rats, it significantly increased the accumulation of the two peptides in the mouse brain. In addition, TP significantly improved cellular uptake of P1 and P2 by brain capillary endothelial cells, indicating that TP enhanced the blood-brain barrier permeation of DWMH-derived peptides. The proposed explanation for the advantage of combined treatment with TP and DWMH in reversing memory impairment was that TP enhanced both the protective effects of DWMH on nerve cells and the accumulation of DWMH in the brain. Our study can aid efforts to develop products and investigate the effects of nutrient combinations on brain disorders.


Assuntos
Camellia sinensis/química , Juglans/química , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Humanos , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , Camundongos , Nozes/química , Ratos , Ratos Sprague-Dawley , Escopolamina/efeitos adversos
3.
Eur J Med Chem ; 185: 111777, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670201

RESUMO

Alzheimer's disease is a common neurodegenerative disease characterized by progressive degeneration and neuronal cell death, resulting in neural network dysfunction. As the underlying mechanisms, oxidative damage and neuroinflammation have been reported to contribute to the onset and deterioration of Alzheimer's disease. The nuclear factor E2-related factor 2-antioxidant responsive element signaling pathway is a pivotal cellular defense mechanism against oxidative stress. Nrf2, a transcription factor, regulates the cellular redox balance and is primarily involved in anti-inflammatory responses. In this study, we synthesized novel chalcone derivatives and found a highly potent Nrf2 activator, compound 20a. Compound 20a confirmed to activate Nrf2 and induce expression of the Nrf2-dependent enzymes HO-1 and GCLC at both mRNA and protein levels. It also suppressed the production of nitric oxide and downregulated inflammatory mediators in BV-2 microglial cells. We found that compound 20a effectively increased the expression level and the activity of superoxide dismutase in both BV-2 microglial cells and brain hippocampus region of the scopolamine-induced mouse model. In addition, compound 20a effectively recovered the learning and memory impairment in a scopolamine-induced mouse model.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Chalcona/farmacologia , Modelos Animais de Doenças , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chalcona/síntese química , Chalcona/química , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Escopolamina , Relação Estrutura-Atividade
4.
Eur J Med Chem ; 183: 111737, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581002

RESUMO

A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50 = 1.3 ±â€¯0.01 µM) and butyrylcholinesterase (IC50 = 1.2 ±â€¯0.09 µM). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57 ±â€¯0.01 µM. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced Aß1-42 aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu2+-induced Aß1-42 aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, Aß1-42 and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD.


Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/metabolismo , Chalconas/química , Inibidores da Colinesterase/química , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Chalconas/farmacologia , Quelantes/química , Inibidores da Colinesterase/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cobre/química , Desenho de Drogas , Feminino , Humanos , Masculino , Transtornos da Memória/tratamento farmacológico , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Ligação Proteica , Escopolamina/metabolismo , Relação Estrutura-Atividade
5.
Life Sci ; 238: 116898, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610193

RESUMO

AIMS: Learning and memory impairment is a common symptom in the early stages of various types of dementia. It is likely to reduce the incidence of dementia with correct intervention. α-Asarone is the main bioactive substance isolated from Acorus tatarinowii Schott and has been proven to improve memory dysfunction; however, at present, the specific underlying mechanism is poorly understood. The aim of the present study was to investigate the effect of α-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. MAIN METHODS: A mouse model of impaired learning and memory was created by ethanol (2.0 g/kg, i.g.). α-Asarone (7.5, 15 or 30 mg/kg, i.p.) was delivered 10 min prior to ethanol administration. The behavioral effect of α-asarone was evaluated using the novel object recognition test. Glutamate (Glu) and γ-aminobutyric acid (GABA) levels in the hippocampus were determined by ELISA, and the protein expression levels of hippocampal GluR2, NMDAR2B, SYNΙ, GLT-1 and CaMKⅡ were detected by western blotting. KEY FINDINGS: Pretreatment with α-asarone significantly improved the behavioral performance, regulated the imbalance of Glu and GABA in the hippocampus and the abnormal expression of related proteins. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu. SIGNIFICANCE: Our results show that the improvement in learning and memory elicited by α-asarone may providing a possible novel candidate for the prevention of learning and memory impairment in the early stages of dementia.


Assuntos
Anisóis/farmacologia , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Fibrinolíticos/farmacologia , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Animais , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo
6.
Planta Med ; 85(17): 1363-1373, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31618776

RESUMO

Lespedeza bicolor, a traditional herbal medicine widely used in Australia, North America, and Eastern Asia, has various therapeutic effects on inflammation, nephritis, hyperpigmentation, and diuresis. In this study, to evaluate the effects of L. bicolor on cognitive function, we examined whether L. bicolor improved amyloid beta-induced memory impairment and assessed the possible mechanisms in mice. Catechin, rutin, daidzein, luteolin, naringenin, and genistein were identified in the powdered extract of L. bicolor by HPCL-DAD analyses. In behavioral experiments, L. bicolor (25 and 50 mg/kg, p. o.) significantly improved amyloid beta25 - 35 (6 nmol, intracerebroventricular)-induced cognitive dysfunction in the Y-maze, novel recognition, and passive avoidance tests. Our molecular studies showed L. bicolor (25 and 50 mg/kg, p. o.) significantly recovered the reduced glutathione content as well as increased thiobarbituric acid reactive substance and acetylcholinesterase activities in the hippocampus. Furthermore, we found that L. bicolor significantly increased the expression of brain-derived neurotrophic factor, and phospho-Akt, extracellular signal-regulated kinase, and cAMP response element binding caused by amyloid beta25 - 35 in the hippocampus. In conclusion, L. bicolor exerts a potent memory-enhancing effect on cognitive dysfunction induced by amyloid beta25 - 35 in mice.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Lespedeza/química , Transtornos da Memória/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Peptídeos beta-Amiloides , Animais , Cognição/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Fragmentos de Peptídeos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
7.
Biol Pharm Bull ; 42(8): 1384-1393, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366873

RESUMO

We previously demonstrated that Bacopa monnier (L.) WETTST. extract (BME) ameliorated cognitive dysfunction in animal models of dementia by enhancing synaptic plasticity-related signaling in the hippocampus and protecting cholinergic neurons in the medial septum. To further clarify the pharmacological features and availability of BME as a novel anti-dementia agent, we investigated whether BME affects neuronal repair using a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampus. Mice pretreated with TMT (2.8 mg/kg, intraperitoneally (i.p.)) on day 0 were given BME (50 mg/kg, per os (p.o.)) once daily for 15-30 d. Cognitive performance of the animals was elucidated twice by the object location test and modified Y maze test on days 17-20 (Phase I) and days 32-35 (Phase II) or by the passive avoidance test on Phase II. TMT impaired hippocampus-dependent spatial working memory and amygdala-dependent fear-motivated memory. The administration of BME significantly prevented TMT-induced cognitive deficits. The protective effects of BME on the spatial memory deficits were confirmed by Nissl staining of hippocampal tissues and propidium iodide staining of organotypic hippocampal slice cultures. Immunohistochemical studies conducted on days 17 and 32 revealed that thirty days of treatment with BME increased the number of 5-bromo-2'-deoxyuridine (BrdU)-immunopositive cells in the dentate gyrus region of TMT-treated mice, whereas fifteen days of treatment with BME had no effect. These results suggest that BME ameliorates TMT-induced cognition dysfunction mainly via protecting the hippocampal neurons from TMT-induced hippocampal lesions and partly via promoting neuroregeneration in the dentate gyrus regions.


Assuntos
Bacopa , Disfunção Cognitiva/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Transtornos da Memória/patologia , Camundongos , Regeneração Nervosa/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Síndromes Neurotóxicas/patologia , Compostos de Trimetilestanho
8.
Phytother Res ; 33(10): 2692-2701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364205

RESUMO

Verbascoside is a water-soluble natural phenylethanoid glycoside and distributes widely in plants. It has been proved with antioxidant, neuroprotective, anti-inflammatory, antibacterial, and immunomodulatory bioactivities. In this experiment, the effect and mechanism of verbascoside on hypoxic memory injury were studied in a low-pressure and low-oxygen chamber. Verbascoside (50, 150, and 300 mg/kg) was intragastrically administered once a day for 7 days. On the fourth day, rats were placed in the chamber to simulate a 7,500 m high-altitude environment The eight-arm maze was used to test the memory ability. The levels of MDA, GSH, and T-SOD in plasma, brain-NH, and hippocampus were detected. The mRNA expression of mTOR, P70S6K, and 4E-BP1 in the hippocampus tissue was determined by PCR. The protein expression of P-mTOR, P-P70S6K, P-4E-BP1, and Cleaved Caspase-3 in the hippocampus tissue was determined by western blot. The results indicated that administration with verbascoside could obviously reduce the working memory error, reference memory error, total errors, and total time; relieve the neuron damage in CA1 region of the hippocampus; and decrease the oxidative stress correlation enzyme activity in plasma, brain, and hippocampus. The amelioration of verbascoside on high altitude-induced memory impairment may be associated with the adjustment of oxidative stress and mTOR signaling pathway.


Assuntos
Altitude , Glucosídeos/farmacologia , Transtornos da Memória/tratamento farmacológico , Fenóis/farmacologia , Animais , Glucosídeos/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipóxia , Masculino , Transtornos da Memória/etiologia , Fenóis/uso terapêutico , Ratos , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo
9.
Int J Mol Sci ; 20(14)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31331043

RESUMO

We explored the preventative effect of Annona atemoya leaf (AAL) extract on memory impairment in a scopolamine (SCO)-induced cognitive deficit mouse model. Fifty-eight mice were randomly divided into six groups and orally treated with AAL extract at (50, 100, or 200 mg/kg) or tacrine (TAC) for 21 days. Memory deficits were induced by a single injection of 1 mg/kg SCO (i.p.) and memory improvement was evaluated by using behavioral tests such as the passive avoidance task and Y-maze test. The levels of cholinergic functions, neuronal cell death, reactive oxygen species, and protein expression related to hippocampal neurogenesis were examined by immunohistochemical staining and western blotting. The administration of AAL extract improved memory impairment according to increased spontaneous alternation in the Y-maze and step-through latency in passive avoidance test. AAL extract treatment increased the acetylcholine content, choline acetyltransferase, and acetylcholinesterase activity in the hippocampus of SCO-stimulated mice. In addition, AAL extract attenuated oxidative stress-induced neuronal cell death of hippocampal tissue. In terms of the regulatory mechanisms, AAL extract treatment reversed the SCO-induced decreases in the expression of Akt, phosphorylation of cAMP response element binding protein, and brain-derived neurotrophic factor. Our findings demonstrate that AAL extract has the ability to alleviate memory impairment through preventative effect on cholinergic system dysfunction and oxidative stress-related neuronal cell death in a SCO-induced memory deficit animal model. Overall, AAL may be a promising plant resource for the managing memory dysfunction due to neurodegenerative diseases, such as Alzheimer's disease (AD).


Assuntos
Annona/química , Neurônios Colinérgicos/efeitos dos fármacos , Neurônios Colinérgicos/metabolismo , Transtornos da Memória/metabolismo , Extratos Vegetais/farmacologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Escopolamina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Camundongos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química
10.
Phytomedicine ; 63: 153007, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301537

RESUMO

BACKGROUND: Aerial parts of Peganum harmala Linn is used as a traditional medical herb for treatment of amnesia in Uighur medicine in China. Deoxyvasicine (DVAS) is one of the chief active ingredients in P. harmala, it possesses strong acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in vitro, but the therapeutic effect and mechanisms on amnesia in vivo are unclear. PURPOSE: The objective of this study was to investigate the improvement effect of DVAS from P. harmala in learning and memory deficits of scopolamine-induced mice and elucidate the underlying mechanisms involved. METHODS: Mice were pretreated with DVAS (5, 15 and 45 mg/kg) and huperzine-A (0.2 mg/kg) by gavage for 7 days, and subsequently were daily intraperitoneally injected with scopolamine (1 mg/kg) to induce learning and memory deficits and behavioral performance was assessed by Morris water maze. To further evaluate the potential mechanisms of DVAS in improving learning and memory capabilities, pathological change, levels of various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation were examined. RESULTS: The results showed that DVAS could alleviate learning and memory deficits in scopolamine-treated mice. DVAS could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities and protein expressions. DVAS could induce brain-derived neurotrophic factor and protect hippocampal pyramidal cells against neuronal damage. DVAS also enhanced antioxidant defense via increasing the antioxidant enzyme level and activity of glutathione peroxidase, and anti-inflammatory function through suppressing tumor necrosis factor-α. Additionally, DVAS could regulate the neurotransmitters by elevating acetylcholine, 5-hydroxytryptamine, γ-aminobutyric acid and reducing 5-hydroxyindole-3-acetic acid and glutamic acid. CONCLUSION: Results illustrated that DVAS may be a promising candidate compound against amnesia via restoration of cholinergic function, regulating neurotransmitters, attenuating neuroinflammation and oxidative stress.


Assuntos
Alcaloides/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Quinazolinas/farmacologia , Acetilcolina/metabolismo , Amnésia/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Inibidores da Colinesterase/farmacologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peganum/química , Escopolamina/toxicidade , Sesquiterpenos/farmacologia
11.
Neurochem Res ; 44(8): 1851-1868, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31187398

RESUMO

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg-1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1ß, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi.


Assuntos
Melatonina/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Regulação para Baixo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Transtornos da Memória/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos Wistar , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos
12.
Molecules ; 24(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174251

RESUMO

Ginseng has been used to alleviate age-related dementia and memory deterioration for thousands of years. This study investigated the protective effect of red ginseng saponins against scopolamine-induced cerebral injury. Meanwhile, pharmacokinetics of ginsenosides in normal and scopolamine-treated rats were compared. After scopolamine injection, glutathione, catalase and superoxide dismutase levels were significantly decreased when compared with control group. Compared with SA group, pretreatment of rats with red ginseng saponins could increase glutathione, catalase and superoxide dismutase level. Treatment with red ginseng saponins significantly decreased malondialdehyde level. In the pharmacokinetic analysis, a pattern recognition analysis method was used to investigate the pharmacokinetics of the absorbed compounds in blood. The pharmacokinetic parameters of Rg1, Rg2, Rh3, Rg5 and Rk1 in model group had higher area under the curve (AUC), mean residence time (MRT) and peak plasma concentration (Cmax) values; area under the curve (AUC) values and peak plasma concentration (Cmax) of model group was significantly different from that of normal group (p < 0.05). The Cmax value of Rk3, Rh1, Rh2 and Rh4 in model group was higher than normal group, but their AUC values were not significantly different. There was no significantly difference in time at Cmax (Tmax), AUC and Cmax values of Rb1, Rb2 Re, Rc, Rd and Rf between the model and normal group. 16 ginsenosides were grouped into three separate clusters according to principal component analysis (PCA) score plot based on pharmacokinetic data. The results suggested red ginseng saponins have significant protective effect against scopolamine-induced memory deficit and scopolamine-induced rats could lead to the changes of pharmacokinetic behaviors of ginsenosides.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Panax/química , Saponinas/farmacologia , Animais , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/patologia , Humanos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Fármacos Neuroprotetores/farmacocinética , Ratos , Ratos Sprague-Dawley , Saponinas/química , Saponinas/farmacocinética , Escopolamina/toxicidade
13.
Food Funct ; 10(6): 3650-3659, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31165850

RESUMO

Cholinergic dysfunction and oxidative stress are the most common causes of Alzheimer's disease (AD). Safflower seed contains various anti-oxidant and cholinergic improvement compounds, such as serotonin and its derivatives. In the present study, we investigated the protective effects and mechanisms of a safflower seed extract on scopolamine-induced memory impairment in a mouse model. The safflower seed extract was orally administered at a dose of 100 mg kg-1 day-1, and then behavior tests (such as T-maze and novel object recognition tests) were conducted. Acetyl cholinesterase (AChE) activity, reactive oxygen species (ROS) production, and antioxidant enzymes in the brain were measured. In behavior tests, the novel route exploration and object recognition were improved by the administration of the safflower seed extract, which suggests that the safflower seed extract improves memory function in the scopolamine-treated mouse model. In addition, the safflower seed extract-administered group showed inhibition of the AChE activity and improved cholinergic dysfunction. Furthermore, the administration of the safflower seed extract resulted in lower ROS production and higher antioxidant enzyme levels as compared to the scopolamine-treated group, suggesting the protective role of the safflower seed extract against oxidative stress. The results of the present study suggest that the safflower seed extract improves scopolamine-induced memory deficits via the inhibition of cholinergic dysfunction and oxidative stress. Therefore, safflower seeds might become a promising agent for memory improvement in AD patients.


Assuntos
Carthamus tinctorius/química , Colinérgicos/administração & dosagem , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Acetilcolinesterase/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos ICR , Espécies Reativas de Oxigênio/metabolismo , Escopolamina/efeitos adversos , Sementes/química
14.
Life Sci ; 231: 116532, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31170417

RESUMO

AIMS: It is a promising approach to search the therapeutic strategies for treating lead (Pb) toxicity. Allicin, a natural compound extracted from Allium sativum (garlic), has been reported to have many beneficially biological properties. In this study, we investigated the protective effects of allicin on learning and memory function of rats exposed by lead acetate at developmental stage. MATERIALS AND METHODS: Rats received lead acetate for inducing toxicity, and gavaged with allicin to ameliorate this toxicity. Morris water maze test was performed to determine learning and memory function. Superoxide dismutase (SOD), glutathione (GSH) and methane dicarboxylic aldehyde (MDA) was measured to determine oxidative stress. Immunofluorescence was carried out to analyze GFAP-positive cells. The protein expression of ERK, p-ERK, EGFR and p-EGFR were detected using western blot. KEY FINDINGS: We found that allicin ameliorated lead acetate-caused learning and memory deficits by promoting hippocampus astrocyte differentiation, which mainly through EGFR/ERK signaling. Moreover, allicin attenuated the increased ROS level by regulating the oxidative defense system. SIGNIFICANCE: These results suggest that allicin is a potent agent able to ameliorate lead acetate-induced learning and memory deficits during early development, and may thus be useful for defeating lead acetate toxicity.


Assuntos
/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Ácidos Sulfínicos/farmacologia , Animais , Antioxidantes/farmacologia , Feminino , Glutationa/metabolismo , Hipocampo/metabolismo , Chumbo/efeitos adversos , Intoxicação por Chumbo/tratamento farmacológico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Compostos Organometálicos/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Wistar , Ácidos Sulfínicos/metabolismo , Superóxido Dismutase/metabolismo
15.
Biomed Pharmacother ; 117: 109077, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177064

RESUMO

BACKGROUND: Prenatal stress (PS) leads to a wide variety of behavioral and emotional aberration observed in later life, particularly in the impairment of spatial learning and memory in offspring. Icariin (ICA) is a naturally occurring furanocoumarin and exhibits many pharmacological properties, including potent improvement on learning and memory. PURPOSE: We pretend to investigate the improvement of ICA on learning and memory impairment in PS. METHODS: Female PS offspring rats were used to explore the effects of ICA on learning and memory impairment. After 28 days of ICA (20, 40 and 80 mg/kg/day) treatment, we measured Morris water maze and 8-Arm Maze, the HPA axis and the related pathway in the hippocampus. RESULTS: We reported that ICA ameliorated the spatial learning and memory and working memory impairment in the female offspring rats. Correspondingly, ICA prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus. ICA significantly decreased the serum adrenocorticotropin, corticotropin-releasing hormone and corticosterone levels in offspring rats exposed to PS, associated with increased GR expression. Additionally, ICA treatment significantly increased the neurogranin (Ng) and c-fos protein expression of hippocampus in the offspring rats. Furthermore, the protein of relative content of p-EKR/ERK, p-CaMKIIα/CaMKIIα, p-CREB/CREB were remarkably increased after ICA treatment in the offspring rats. CONCLUSION: Taken together, ICA may be an effective therapeutic for learning and memory dysfunction in female offspring exposed to PS, its neuroprotective effect was mediated in part by normalizing the HPA axis and up-regulating of ERK/CaMKIIα/CREB signaling, Ng and c-fos protein.


Assuntos
Flavonoides/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Animais , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo
16.
Adv Gerontol ; 32(1-2): 121-127, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31228377

RESUMO

The course intake of the nutritional supplement «Kardisten¼ normalizes increased levels of cortisol in the blood, optimizes the activity of the vessels of the brain, improving the functional state and leading to an increase in the productivity of short-term and long-term memory, more pronounced in the group of persons up to 50. At initial organic changes in the brain vessels, «Kardisten¼ significantly reduces the level of cortisol, increases to a greater extent the productivity of memory than at atherosclerosis. «Kardisten¼ activates the natural mechanisms of increasing the functional capabilities of an organism, exerting a beneficial effect on the body of adults and the elderly people, and can be recommended for the correction of physical, mental health and preservation of active longevity.


Assuntos
Transtornos da Memória , Memória , Saúde Mental , Extratos Vegetais , Adulto , Idoso , Encéfalo/efeitos dos fármacos , Humanos , Hidrocortisona , Longevidade , Transtornos da Memória/tratamento farmacológico , Extratos Vegetais/uso terapêutico
17.
Int J Neurosci ; 129(10): 1024-1038, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31215278

RESUMO

Aim: The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone on the brain tissues oxidative damage and learning and memory impairment in the juvenile hypothyroid rats was evaluated. Main methods: Rats were classified as: ( 1 ) Control; (2) Propylthiouracil (PTU); (3) PTU-Pio 10 and (4) PTU-Pio 20. PTU was given in drinking water (0.05%) during 6 weeks. Pioglitazone (10 or 20 mg/kg) was daily injected intraperitoneally. Passive avoidance (PA) and Morris water maze (MMW) were conducted. Later, the animals were sacrificed and the brain tissues were removed for biochemical measurements. Key funding: The results indicated that in the MWM escape latency as well as traveled path increased in the PTU group as compared to the control group. Also, the time spent in the target quadrant in the probe test of MWM and step-through latency in the PA test were decreased in the PTU group as compared to the control group. Pioglitazone reversed all the negative behavioral effects of hypothyroidism. Administration of PTU attenuated thiol and superoxide dismutase (SOD), and catalase (CAT) activities in the brain tissues, whereas increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. PPARγ agonist improved thiol, SOD and CAT, while diminished MDA concentration. Significance: Our finding in the present study indicated that PPARγ agonist pioglitazone prevented the brain tissues from oxidative damage and learning and memory impairments in juvenile hypothyroid rats.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Hipotireoidismo/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , Pioglitazona/farmacologia , Fatores Etários , Animais , Lesões Encefálicas/metabolismo , Relação Dose-Resposta a Droga , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipotireoidismo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/metabolismo , Estresse Oxidativo/fisiologia , Pioglitazona/uso terapêutico , Ratos , Ratos Wistar , Resultado do Tratamento
18.
Mol Med Rep ; 20(1): 332-340, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115535

RESUMO

Saikosaponin­D (SSD), which is the main bioactive component in the traditional Chinese medicine Chai Hu (Bupleurum falcatum L), possesses estrogen­like properties and is widely used in treating estrogen­related neurological disorders. The current study aimed to investigate the protective effects of SSD on the fear memory deficit in ovariectomized (OVX) rats and the potential underlying mechanism. SSD treatment significantly prolonged freezing time in OVX rats in a manner similar to that of estradiol (E2), whereas this effect was markedly suppressed by co­administration of ICI182780, a non­selective estrogen receptor (ER) inhibitor. The expression of ERα in the hippocampus of OVX rats was significantly elevated by SSD; however, Erß expression and E2 synthesis were not markedly affected by SSD treatment. Collectively, this study demonstrated that SSD­mediated fear memory improvement in OVX rats may be attributed not to E2 levels or ERß activity, but to ERα activation in the hippocampus.


Assuntos
Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Medo/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , Bupleurum/química , Estradiol/metabolismo , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor beta de Estrogênio/antagonistas & inibidores , Medo/fisiologia , Feminino , Fulvestranto/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Medicina Tradicional Chinesa , Transtornos da Memória/genética , Transtornos da Memória/patologia , Ácido Oleanólico/farmacologia , Ovariectomia , Ratos , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/patologia
19.
Life Sci ; 228: 285-294, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31063733

RESUMO

AIMS: Oxidative stress and apoptosis have major roles in the progression of traumatic brain injury (TBI)-associated motor and cognitive deficits. The present study was aimed to elucidate the putative effects of chrysin, a natural flavonoid compound, against TBI-induced motor and cognitive dysfunctions and possible involved mechanisms. MAIN METHODS: Chrysin (25, 50 or 100 mg/kg) was orally administered to rats starting immediately following TBI induction by Marmarou's weight-drop technique and continuously for 3 or 14 days. Neurological functions, motor coordination, learning and memory performances, histological changes, cell apoptosis, expression of pro- and anti-apoptotic proteins, and oxidative status were assayed at scheduled time points after experimental TBI. KEY FINDINGS: The results indicated that treatment with chrysin improved learning and memory disabilities in passive avoidance task, and ameliorated motor coordination impairment in rotarod test after TBI. These beneficial effects were accompanied by increased the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), decreased malondialdehyde (MDA) content, prevented neuronal loss, diminished apoptotic index, elevated the expression of anti-apoptotic Bcl-2 protein, and reduced the expression of pro-apoptotic Bax protein in the cerebral cortex and hippocampus tissues. SIGNIFICANCE: Our findings suggest that both anti-oxidative and anti-apoptotic properties of chrysin (especially in the dose of 100 mg/kg) are possible mechanisms that improve cognitive/motor deficits and prevent neuronal cell death after TBI.


Assuntos
Antioxidantes/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Flavonoides/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/fisiopatologia , Modelos Animais de Doenças , Flavonoides/administração & dosagem , Aprendizagem/efeitos dos fármacos , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Ratos Wistar
20.
Arch Ital Biol ; 157(1): 24-36, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31111954

RESUMO

N-(p-amylcinnamoyl) anthranilic acid (ACA) is a blocker of transient receptor potential melastatin-2 (TRPM2) which is a non-selective, Ca2+-permeable and oxidative stress sensor cation channel. Intracerebroventricular (ICV) streptozotocin (STZ) induction successfully generates spatial memory deficits in rats. The purpose of this study was to investigate effects of ACA on a rat model of STZ-induced learning and memory deficits. A total of 60 Wistar rats randomly divided into six groups; (1) control, (2) sham-operated, (3) ICV-STZ administered, (4) ICV-STZ + memantine (5 mg/kg i.p.), (5) ICV-STZ + ACA (25 mg/kg i.p.) and (6) a combination therapy group, ICV-STZ + ACA (25 mg/kg) + memantine (5 mg/kg). Effects of the drugs on spatial memory deficits were appraised in Morris water maze (MWM) apparatus. Anxiety-like behavior of the rats were also assessed by using both the elevated plus maze (EPM) and open field maze (OFM) apparatuses. Western blot analysis of hippocampal tissues revealed TRPM2-L channel protein expression levels. Serum levels of tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Memantine treatment ameliorated the spatial memory deficits induced, as evidenced by the MWM tests. However, ACA treatment did not provide any improvement, instead positive effects of memantine were attenuated by ACA treatment. Western blot analysis in hippocampal tissues showed that TRPM2-L protein expression was markedly suppressed in ICV-STZ administered group. The ACA treatment reversed that suppression. Surprisingly, the memantine treatment resulted in overexpression of TRPM2-L, to a certain extent. Examination of the rats in EPM and OFM apparatuses, as a display of anxiety-like behavior, did not reveal any marked difference among groups. Serum levels of TNF-α and MDA also did not vary significantly among groups, as well. Conclusively, our findings showed for the first time that TRPM2-L protein expression was significantly suppressed in the ICV-STZ induced memory deficit model. Even though ACA reversed this suppression, no improvement in spatial memory was observed following ACA treatment.


Assuntos
Memantina , Transtornos da Memória , ortoaminobenzoatos , Animais , Aprendizagem em Labirinto , Memantina/farmacologia , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Wistar , Estreptozocina , Canais de Cátion TRPM/efeitos dos fármacos , ortoaminobenzoatos/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA