Neurotoxicity Research

, Volume 35, Issue 2, pp 373–386 | Cite as

Comparing the Effects of Chlorogenic Acid and Ilex paraguariensis Extracts on Different Markers of Brain Alterations in Rats Subjected to Chronic Restraint Stress

  • María Eduarda de Lima
  • Ana Z. Ceolin Colpo
  • Marisol Maya-López
  • Edgar Rangel-López
  • Hugo Becerril-Chávez
  • Sonia Galván-Arzate
  • Juana Villeda-Hernández
  • Laura Sánchez-Chapul
  • Isaac Túnez
  • Vanderlei Folmer
  • Abel SantamaríaEmail author


Positive influence of yerba mate (Ilex paraguariensis) on human health issues has been attributed to its frequent consumption in South American countries and is assumed to be due to its high content of antioxidant compounds, including chlorogenic acid (CGA); however, hard evidence about its positive effects under chronic stress conditions is still required. In this study, the effects of yerba mate extracts (IpE), and its main compound chlorogenic acid (CGA), on behavioral and morphological endpoints of brain damage induced by chronic restraint stress (CRS) to rats were evaluated and compared. CRS sessions were performed during 21 days. IpE (200 mg/mL, p.o.) or CGA (2 mg/mL, p.o.) were administered daily 30 min before stress. Behavioral tests comprised motor skills and anxiety-like activity. Histological (H&E) and histochemical changes were explored in three brain regions: cortex (Cx), hippocampus (Hp), and striatum (S). Rats subjected to CRS exhibited hypoactive patterns of locomotor activity. Rats receiving IpE before CRS preserved the basal locomotor activity. Stressed animals also augmented the anxiety-like activity, whereas IpE normalized exploratory behavior. Stressed animals presented cell damage in all regions. Morphological damage was more effectively prevented by IpE than CGA. Stressed animals also augmented the expression/localization pattern of the tumor necrosis factor alpha in the striatum and the expression of the glial fibrillary acidic protein in the hippocampus (stratum moleculare) and cortex, whereas IpE and CGA reduced the expression of these molecules. In turn, CGA exhibited only moderate protective effects on all markers analyzed. Our findings support a protective role of IpE against CRS, which may be related to the antioxidant and anti-inflammatory properties of its compounds. Since CGA was unable to prevent all the alterations induced by CRS, it is concluded that the protective properties of the whole extract of Ilex paraguariensis are the result of the combined effects of all its natural antioxidant compounds, and not only of the properties of CGA.


Brain damage Oxidative stress Brain regions Inflammation Antioxidant defense Natural antioxidant compounds 



The authors express gratitude to Rocío Morales-Bárcenas from the Instituto Nacional de Cancerología for her excellent technical assistance.

Authors’ Contributions

ME de Lima, AC Colpo, M Maya-López, E Rangel-López, L Sánchez-Chapul, H Becerril-Chávez, S Galván-Arzate, and J Villeda-Hernández contributed to the project’s development, data collection, and analysis. ME de Lima and A Santamaría wrote the manuscript. ME de Lima, V Folmer, and A Santamaría designed the whole project. All authors have approved the final manuscript.


This work was supported by CAPES (Grant No. 99999.006894/2015-01, MEL), UNIPAMPA (MEL and AZCC, Brazil), and CONACyT (Grant No. 205648, AS, Mexico).

Compliance with Ethical Standards

Ethical Approval

The care and handling of all animals were carried out in accordance with the guidelines of the Guide of the National Institutes of Health for the Care and Use of Laboratory Animals NOM-062-ZOO 1999, as well as the Local Committee of Bioethics of the Instituto Nacional de Neurología and Neurocirugía (Mexico) established upon approval of the Mexican Ministry of Health.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • María Eduarda de Lima
    • 1
    • 2
  • Ana Z. Ceolin Colpo
    • 1
    • 2
  • Marisol Maya-López
    • 1
  • Edgar Rangel-López
    • 1
  • Hugo Becerril-Chávez
    • 1
  • Sonia Galván-Arzate
    • 3
  • Juana Villeda-Hernández
    • 4
  • Laura Sánchez-Chapul
    • 5
  • Isaac Túnez
    • 6
  • Vanderlei Folmer
    • 2
  • Abel Santamaría
    • 1
    Email author
  1. 1.Laboratorio de Aminoácidos ExcitadoresInstituto Nacional de Neurología y NeurocirugíaMexico CityMexico
  2. 2.Programa de Pós-Graduação em BioquímicaUniversidade Federal do Pampa (UNIPAMPA)UruguaianaBrazil
  3. 3.Departamento de NeuroquímicaInstituto Nacional de Neurología y NeurocirugíaMexico CityMexico
  4. 4.Laboratorio de Patología ExperimentalInstituto Nacional de Neurología y NeurocirugíaMexico CityMexico
  5. 5.Servicio de NeurocienciasInstituto Nacional de RehabilitaciónMexico CityMexico
  6. 6.Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Enfermería/Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de CórdobaCordobaSpain

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