Efeito neuroprotetor da Berberina na neurotoxicidade induzida por estreptozotocina e lipolissacarídeo em ratos
Autor(a) principal: | |
---|---|
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 |