Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos

Detalhes bibliográficos
Autor(a) principal: Oliveira, Juliana Sorraila de
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/21706
Resumo: Alzheimer's disease (AD) is considered the major cause of dementia and is characterized by changes in the cholinergic and purinergic system, oxidative stress, inflammatory process and metabolic changes that, in turn, are responsible for brain cell death with consequent memory loss and other significant symptoms. On the other hand, Berberine (BRB), an alkaloid widely used in traditional Chinese medicine has had significant effects on neurodegenerative diseases, including AD. The benefits described by the use of BRB concern, among others, its antioxidant, anti-inflammatory and neuroprotective ability. Thus, the aim of the present study was to investigate the effects of BRB on memory and to relate these changes with the cholinergic system, purinergic system and oxidative stress through two experimental rat models widely used in the investigation of AD candidate compounds. Therefore, the first investigation was through the study of BRB at doses of 50 and 100 mg/kg on the model of dementia induced by intracerebroventricular injection of streptozotocin (ICV-STZ). The rats were submitted to ICV-STZ 3 mg/kg or saline solution and, 3 days later, BRB treatments at 50 or 100 mg/kg or saline for 21 days were started. Behavioral assessment of memory as well as oxidative stress parameters and activity of ectoenzymes in samples of cerebral cortex and hippocampus were investigated.. The results demonstrated that BRB at both doses was effective in protecting against memory impairment, oxidative stress and decreased activity of the enzymes NTPDase, 5'-Nucleotidase and adenosine deaminase. The second study concerns the analysis of BRB on the experimental model of lipopolysaccharide-induced neuroinflammation (LPS). The animals were submitted for 8 consecutive days to an injection (ip) per day of LPS at a dose of 250 μg / kg body weight and BRB at a dose of 50 mg/kg was administered orally 30 minutes after LPS for 8 days. BRB has been shown to be effective in protecting recognition memory, increased acetylcholinesterase activity, oxidative stress and decreased NTPDase and 5'-nucleotidase ectoenzyme activity in cerebral cortex and hippocampus samples from LPS animals. Taken together, we can suggest that BRB has a potent antioxidant activity on Alzheimer's dementia with the potential to modulate cholinergic and purinergic system pathways. In this context, the use of BRB can be pointed as a new therapeutic and multi-target strategy to be considered in the treatment of AD.
id UFSM_fea5791925bc5a44c0b8542b2813394c
oai_identifier_str oai:repositorio.ufsm.br:1/21706
network_acronym_str UFSM
network_name_str Manancial - Repositório Digital da UFSM
repository_id_str
spelling Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratosEvaluation of the Berberina neuroprotector effect on streptozotocin-induced neurotoxicity and lps-induced neuroinflammationCoptis chinensisMemóriaDemênciaSistema colinérgicoSistema purinérgicoEstresse oxidativoMemoryDementiaCholergic systemPurinergic systemOxidative stressCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAlzheimer's disease (AD) is considered the major cause of dementia and is characterized by changes in the cholinergic and purinergic system, oxidative stress, inflammatory process and metabolic changes that, in turn, are responsible for brain cell death with consequent memory loss and other significant symptoms. On the other hand, Berberine (BRB), an alkaloid widely used in traditional Chinese medicine has had significant effects on neurodegenerative diseases, including AD. The benefits described by the use of BRB concern, among others, its antioxidant, anti-inflammatory and neuroprotective ability. Thus, the aim of the present study was to investigate the effects of BRB on memory and to relate these changes with the cholinergic system, purinergic system and oxidative stress through two experimental rat models widely used in the investigation of AD candidate compounds. Therefore, the first investigation was through the study of BRB at doses of 50 and 100 mg/kg on the model of dementia induced by intracerebroventricular injection of streptozotocin (ICV-STZ). The rats were submitted to ICV-STZ 3 mg/kg or saline solution and, 3 days later, BRB treatments at 50 or 100 mg/kg or saline for 21 days were started. Behavioral assessment of memory as well as oxidative stress parameters and activity of ectoenzymes in samples of cerebral cortex and hippocampus were investigated.. The results demonstrated that BRB at both doses was effective in protecting against memory impairment, oxidative stress and decreased activity of the enzymes NTPDase, 5'-Nucleotidase and adenosine deaminase. The second study concerns the analysis of BRB on the experimental model of lipopolysaccharide-induced neuroinflammation (LPS). The animals were submitted for 8 consecutive days to an injection (ip) per day of LPS at a dose of 250 μg / kg body weight and BRB at a dose of 50 mg/kg was administered orally 30 minutes after LPS for 8 days. BRB has been shown to be effective in protecting recognition memory, increased acetylcholinesterase activity, oxidative stress and decreased NTPDase and 5'-nucleotidase ectoenzyme activity in cerebral cortex and hippocampus samples from LPS animals. Taken together, we can suggest that BRB has a potent antioxidant activity on Alzheimer's dementia with the potential to modulate cholinergic and purinergic system pathways. In this context, the use of BRB can be pointed as a new therapeutic and multi-target strategy to be considered in the treatment of AD.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA Doença de Alzheimer (DA) é considerada a maior causa de demência e caracterizada por apresentar alterações dos sistemas colinérgico e purinérgico, estresse oxidativo, processo inflamatório e mudanças metabólicas que, por sua vez, são responsáveis pela morte celular cerebral com consequente perda de memória e outros sintomas significativos. Por outro lado, a Berberina (BRB), um alcaloide muito utilizado na Medicina Tradicional Chinesa tem apresentado efeitos significativos em doenças neurodegenerativas, entre elas, a DA. Os benefícios descritos pelo uso da BRB dizem respeito, dentre outras, à sua capacidade antioxidante, anti-inflamatória e neuroprotetora. Sendo assim, o objetivo do presente estudo foi investigar os efeitos da BRB sobre a memória e relacionar estas mudanças com os sistemas colinérgico e purinérgico e estresse oxidativo através de dois modelos experimentais em ratos muito utilizados na investigação de compostos candidatos ao tratamento da DA. Para tanto, investigou-se primeiramente o efeito da BRB nas doses de 50 e 100 mg/kg sobre o modelo de demência induzido pela injeção intracerebroventricular de streptozotocina (ICV-STZ). Os ratos foram submetidos a ICV-STZ (3 mg/kg) ou solução salina e, 3 dias depois, iniciou-se o tratamento com BRB nas doses de 50 ou 100 mg/kg ou solução salina durante 21 dias. A avaliação comportamental da memória, bem como, parâmetros de estresse oxidativo e atividade de ectoenzimas em amostras de córtex cerebral e hipocampo foram investigados. Os resultados demonstraram que a BRB em ambas as doses foi eficaz na proteção contra o comprometimento da memória, o estresse oxidativo e a diminuição na atividade das enzimas NTPDase, 5’-Nucleotidase e adenosina desaminase (ADA). Posteriormente, investigou-se a ação da BRB em um modelo experimental de neuroinflamação induzido por lipopolissacarídeo (LPS). Os ratos foram submetidos por 8 dias consecutivos a uma injeção (ip) diária de LPS na dose de 250 ug/kg do peso corporal e a BRB na dose de 50 mg/kg administrada via oral 30 minutos após o LPS. A BRB demonstrou eficácia na proteção da memória de reconhecimento, no aumento da atividade da acetilcolinesterase, na proteção contra o estresse oxidativo e na diminuição da atividade das ectoenzimas NTPDase e 5'-nucleotidase em amostras de córtex cerebral e hipocampo dos ratos submetidos à injeção de LPS. Diante dos resultados apresentados, podemos sugerir que a BRB possui uma potente atividade antioxidante prevenindo a demência do tipo Alzheimer além de uma potencial atividade moduladora sobre as vias do sistema colinérgico e purinérgico. Nesse contexto, o uso da BRB pode ser apontado como uma nova estratégia terapêutica e multialvo a ser considerada no tratamento da DA.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasAndrade, Cinthia Melazzo dehttp://lattes.cnpq.br/2886709251370905Chitolina, Maria RosaSpanevello, Roselia MariaStefanello, Francieli MoroSagrillo, Michele RoratoOliveira, Juliana Sorraila de2021-08-03T17:53:43Z2021-08-03T17:53:43Z2019-10-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/21706porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-09-29T19:46:43Zoai:repositorio.ufsm.br:1/21706Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-09-29T19:46:43Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
Evaluation of the Berberina neuroprotector effect on streptozotocin-induced neurotoxicity and lps-induced neuroinflammation
title Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
spellingShingle Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
Oliveira, Juliana Sorraila de
Coptis chinensis
Memória
Demência
Sistema colinérgico
Sistema purinérgico
Estresse oxidativo
Memory
Dementia
Cholergic system
Purinergic system
Oxidative stress
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
title_full Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
title_fullStr Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
title_full_unstemmed Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
title_sort Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
author Oliveira, Juliana Sorraila de
author_facet Oliveira, Juliana Sorraila de
author_role author
dc.contributor.none.fl_str_mv Andrade, Cinthia Melazzo de
http://lattes.cnpq.br/2886709251370905
Chitolina, Maria Rosa
Spanevello, Roselia Maria
Stefanello, Francieli Moro
Sagrillo, Michele Rorato
dc.contributor.author.fl_str_mv Oliveira, Juliana Sorraila de
dc.subject.por.fl_str_mv Coptis chinensis
Memória
Demência
Sistema colinérgico
Sistema purinérgico
Estresse oxidativo
Memory
Dementia
Cholergic system
Purinergic system
Oxidative stress
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
topic Coptis chinensis
Memória
Demência
Sistema colinérgico
Sistema purinérgico
Estresse oxidativo
Memory
Dementia
Cholergic system
Purinergic system
Oxidative stress
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Alzheimer's disease (AD) is considered the major cause of dementia and is characterized by changes in the cholinergic and purinergic system, oxidative stress, inflammatory process and metabolic changes that, in turn, are responsible for brain cell death with consequent memory loss and other significant symptoms. On the other hand, Berberine (BRB), an alkaloid widely used in traditional Chinese medicine has had significant effects on neurodegenerative diseases, including AD. The benefits described by the use of BRB concern, among others, its antioxidant, anti-inflammatory and neuroprotective ability. Thus, the aim of the present study was to investigate the effects of BRB on memory and to relate these changes with the cholinergic system, purinergic system and oxidative stress through two experimental rat models widely used in the investigation of AD candidate compounds. Therefore, the first investigation was through the study of BRB at doses of 50 and 100 mg/kg on the model of dementia induced by intracerebroventricular injection of streptozotocin (ICV-STZ). The rats were submitted to ICV-STZ 3 mg/kg or saline solution and, 3 days later, BRB treatments at 50 or 100 mg/kg or saline for 21 days were started. Behavioral assessment of memory as well as oxidative stress parameters and activity of ectoenzymes in samples of cerebral cortex and hippocampus were investigated.. The results demonstrated that BRB at both doses was effective in protecting against memory impairment, oxidative stress and decreased activity of the enzymes NTPDase, 5'-Nucleotidase and adenosine deaminase. The second study concerns the analysis of BRB on the experimental model of lipopolysaccharide-induced neuroinflammation (LPS). The animals were submitted for 8 consecutive days to an injection (ip) per day of LPS at a dose of 250 μg / kg body weight and BRB at a dose of 50 mg/kg was administered orally 30 minutes after LPS for 8 days. BRB has been shown to be effective in protecting recognition memory, increased acetylcholinesterase activity, oxidative stress and decreased NTPDase and 5'-nucleotidase ectoenzyme activity in cerebral cortex and hippocampus samples from LPS animals. Taken together, we can suggest that BRB has a potent antioxidant activity on Alzheimer's dementia with the potential to modulate cholinergic and purinergic system pathways. In this context, the use of BRB can be pointed as a new therapeutic and multi-target strategy to be considered in the treatment of AD.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-29
2021-08-03T17:53:43Z
2021-08-03T17:53:43Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/21706
url http://repositorio.ufsm.br/handle/1/21706
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Centro de Ciências Naturais e Exatas
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Centro de Ciências Naturais e Exatas
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
_version_ 1805922095428796416