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1.
J Pharm Pharmacol ; 72(8): 1119-1132, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32363579

RESUMO

OBJECTIVES: To examine the ability of Cassia tora extract to produce, in vitro and in vivo, beneficial effects with respect to events occurring during Alzheimer's disease. METHODS: Previously characterised methanol extract of C. tora was tested for its ability to lessen Aß42 aggregation processes in vitro and to alleviate aluminium-induced impairments in vivo in rats. KEY FINDINGS: Cassia tora extract prevents the aggregation of monomeric, oligomeric and fibrillary Aß1-42 in vitro. Moreover, the daily ingestion of 100 and 400 milligrams of the extract per kilogram of body weight for 60 days ameliorates the neurobehavioral and cognitive abilities of aluminium-treated rats in vivo. Importantly, treatments with the extract trigger a significant recovery of antioxidant enzymes function, a diminution of lipid peroxidation and acetylcholinesterase activity, a decrease of pro-inflammatory cytokines expression and an increase of brain-derived neurotrophic factor levels in both the hippocampus and the frontal cortex. Finally, we evidence that the extract is able to ameliorate the aluminium-dependent loss of neuronal integrity in the CA1 and CA3 regions of the hippocampus. CONCLUSIONS: Altogether, our results reveal that methanol extract of C. tora is able to prevent typical AD-related events and therefore stands as a promising mild and natural anti-AD multitarget compound.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Cassia , Hipocampo/efeitos dos fármacos , Degeneração Neural , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Fragmentos de Peptídeos/metabolismo , Extratos Vegetais/farmacologia , Cloreto de Alumínio , Animais , Comportamento Animal/efeitos dos fármacos , Cassia/química , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Agregados Proteicos , Agregação Patológica de Proteínas , Ratos Wistar
2.
Pharmacol Rep ; 71(6): 1151-1159, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31655280

RESUMO

BACKGROUND: Alzheimer's is a complex neurodegenerative disease and is characterized by extraneuronal accumulation of ß-amyloid peptide. Because of its complex nature, multi-target directed ligands (MTDLs) are increasingly being considered as promising anti-Alzheimer therapeutic agents. This study is aimed at determining the effects of Cassia tora ethyl acetate fraction on several Alzheimer-associated deleterious events in test tubes as well as in human neuroblastoma SK-N-SH and SH-SY5Y cell lines. METHOD: Ethyl acetate fraction of C. tora was purified by chromatography, characterized by 1H and 13C NMR, and tested for its ability to prevent Aß 1-42 aggregation by thioflavin-T fluorescence and transmission electron microscopy. We also analyzed the intracellular ROS level and cytotoxicity in SK-N-SH and SH-SY5Y cell lines. RESULTS: The extract inhibits the formation of Aß 1-42 aggregation from monomers and oligomers, as also acetylcholinesterase activity, Aß 1-42 -induced cell death, and Aß 1-42 -dependent intracellular ROS production in both SK-N-SH and SH-SY5Y cells. In-depth chromatographic and spectroscopic analysis of the extract revealed that the active molecules are most likely triglycerides of oleic acid (C18H34O2). CONCLUSION: We demonstrate for the first time that Cassia tora fraction prevents Aß 1-42 aggregation, inhibits acetylcholinesterase and alleviates Aß 1-42 -induced oxidative stress in human neuroblastoma cells. We further suggest the possible use of triglycerides of oleic acid as efficient anti-Alzheimer agents.


Assuntos
Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Cassia/química , Morte Celular/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Preparações de Plantas/farmacologia , Doença de Alzheimer/metabolismo , Antioxidantes/metabolismo , Benzotiazóis/farmacologia , Linhagem Celular Tumoral , Humanos , Neuroblastoma/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo
3.
Crit Rev Food Sci Nutr ; 59(18): 2999-3018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29846084

RESUMO

Alzheimer's disease (AD) is characterized by a massive neuronal death causing memory loss, cognitive impairment and behavioral alteration that ultimately lead to dementia and death. AD is a multi-factorial pathology controlled by molecular events such as oxidative stress, protein aggregation, mitochondrial dysfunction and neuro inflammation. Nowadays, there is no efficient disease-modifying treatment for AD and epidemiological studies have suggested that diet and nutrition have a significant impact on the development of this disorder. Indeed, some nutrients can protect all kind of cells, including neurons. As prevention is better than cure, life style improvement, with a special emphasis on diet, should seriously be considered as an anti-AD track and intake of nutrients promoting neuronal health is the need of the hour. Diets rich in unsaturated fatty acids, polyphenols and vitamins have been shown to protect against AD, whereas saturated fatty acids-containing diets deprived of polyphenols promote the development of the disease. Thus, Mediterranean diets, mainly composed of fruits, vegetables and omega-3 fatty acids, stand as valuable, mild and preventive anti-AD agents. This review focuses on our current knowledge in the field and how one can fight this devastating neurodegenerative disorder through the simple proper modification of our life style.


Assuntos
Doença de Alzheimer , Dieta , Fenômenos Fisiológicos da Nutrição , Doença de Alzheimer/dietoterapia , Ansiolíticos/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Humanos , Estado Nutricional , Vitaminas/administração & dosagem
4.
Environ Toxicol Pharmacol ; 58: 202-211, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29408763

RESUMO

Alzheimer's disease (AD) is the most common form of dementia and mainly affects cognitive function of the aged populations. Aluminium, a neurotoxic metal, has been suggested as a contributing factor of AD. Caesalpinia crista is a medicinal plant known for its anti-microbial, anti-inflammatory and anti-oxidant properties. The present study was conducted in order to evaluate the neuroprotective effects of methanolic extracts of C. crista (MECC) on aluminium-induced neurodegeneration in rats. Co-administration with MECC significantly and dose dependently ameliorated the aluminium-dependent cognitive impairment, AChE hyperactivity and oxidative stress in the hippocampus and in the frontal cortex of rat brain. Moreover, MECC reduced the neuronal injury induced by aluminium as shown by the diminution of neuron loss and pyknosis in the CA1 and CA3 regions of the hippocampus. From this study, it is inferred that MECC protect against aluminium-induced behavioral alterations, cognitive function, oxidative stress and neuroinflammation in vivo. Therefore, this plant may serve as a source of natural products having multiple functions and could be utilized as an anti-AD preparation.


Assuntos
Alumínio/toxicidade , Caesalpinia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Catalase/metabolismo , Citocinas/genética , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar
5.
Nat Prod Res ; 32(12): 1476-1480, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28714346

RESUMO

The aim of the present study was to determine whether Cassia tora extracts could reverse the oxidative stress-induced neurodegeneration in a Parkinson's disease in vitro model. The leaves were treated with ethyl acetate (CtEA) or methanol (CtME). The extracts were first analysed by HPLC for their phenolic content and then tested for their neuroprotective effects in human SK-N-SH neuroblastoma cells. Cells were pre-treated with various concentrations of extracts followed by incubation with paraquat (14 µM). Firstly, pre-treatment of SK-N-SH cells with 100 µg/mL of CtEA or CtME significantly reduced the paraquat-induced production of reactive oxygen species. Furthermore, both CtEA and CtME reduced the paraquat-induced apoptosis. Moreover, there was a significant reduction of paraquat-induced DNA damage in SK-N-SH cells pre-treated with CtEA or CtME. Finally, both extracts significantly inhibited paraquat-dependent lipid peroxidation. Altogether, these in vitro data establish C. tora as a possible anti-Parkinson natural remedy.


Assuntos
Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Senna/química , Antiparkinsonianos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Neuroblastoma/patologia , Paraquat/toxicidade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Fenóis/análise , Extratos Vegetais/química , Folhas de Planta/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
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