, Volume 236, Issue 2, pp 641–655 | Cite as

Neuroprotective effects of berberine on recognition memory impairment, oxidative stress, and damage to the purinergic system in rats submitted to intracerebroventricular injection of streptozotocin

  • Juliana Sorraila de OliveiraEmail author
  • Fátima Husein Abdalla
  • Guilherme Lopes Dornelles
  • Taís Vidal Palma
  • Cristiane Signor
  • Jamile da Silva Bernardi
  • Jucimara Baldissarelli
  • Luana Suéling Lenz
  • Vitor Antunes de Oliveira
  • Maria Rosa Chitolina Schetinger
  • Vera Maria Melchiors Morsch
  • Maribel Antonello Rubin
  • Cinthia Melazzo de Andrade
Original Investigation


Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100 mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer’s type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3 mg/kg or saline, and 3 days later, were started on a treatment of BRB or saline for 21 days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5′-nucleotidase (EC-5’-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.


Reactive species Antioxidant Ectoenzymes Alzheimer 


Funding information

This study was supported by Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior on number 88882.182124/2018-01, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and the Federal University of Santa Maria, RS, Brazil, and the FINEP research grant “Rede Instituto Brasileiro de Neurociências (IBNet)”, Instituto Nacional de Ciências Tecnológicas (INCT). All the experiments comply with the current laws of Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Juliana Sorraila de Oliveira
    • 1
    • 2
    Email author
  • Fátima Husein Abdalla
    • 3
  • Guilherme Lopes Dornelles
    • 4
  • Taís Vidal Palma
    • 1
    • 2
  • Cristiane Signor
    • 5
  • Jamile da Silva Bernardi
    • 3
  • Jucimara Baldissarelli
    • 3
  • Luana Suéling Lenz
    • 1
    • 2
  • Vitor Antunes de Oliveira
    • 3
  • Maria Rosa Chitolina Schetinger
    • 3
  • Vera Maria Melchiors Morsch
    • 3
  • Maribel Antonello Rubin
    • 5
  • Cinthia Melazzo de Andrade
    • 4
    • 6
  1. 1.Programa de Pós Graduação em Ciências Biológicas: Bioquímica Toxicológica, Setor de Bioquímica e Estresse Oxidativo do Laboratório de Terapia Celular, Centro de Ciências RuraisUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.Post-Graduation Program in Toxicological BiochemistryDepartment of Chemistry of the Center of Natural and Exact Sciences of the Federal University of Santa MariaSanta MariaBrazil
  3. 3.Programa de Pós Graduação em Ciências Biológicas: Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa MariaSanta MariaBrazil
  4. 4.Programa de Pós graduação em Medicina Veterinária, Centro de Ciência Rurais/Departamento de Clínica de Pequenos Animais, Laboratório de Patologia Clínica Veternária/Hospital VeterinárioUniversidade Federal de Santa MariaSanta MariaBrazil
  5. 5.Programa de Pós Graduação em Ciências Biológicas: Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e ExatasLaboratório de Neuropsicofarmacologia Universidade Federal de Santa MariaSanta MariaBrazil
  6. 6.Department of Small Animal ClinicCenter of Rural Sciences Federal University of Santa MariaSanta MariaBrazil

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