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Comparing the Effects of Ferulic Acid and Sugarcane Aqueous Extract in In Vitro and In Vivo Neurotoxic Models

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Abstract

Molecules exhibiting antioxidant, neuroprotective, and regulatory properties inherent to natural products consumed by humans are gaining attention in biomedical research. Ferulic acid (FA) is a phenolic compound possessing antioxidant and cytoprotective properties. It is found in several vegetables, including sugarcane, where it serves as the main antioxidant component. Here, we compared the antioxidant and cytoprotective effects of FA with those of the total sugarcane aqueous extract (SCAE). Specifically, we assessed biochemical markers of cell dysfunction in rat cortical brain slices and markers of physiological stress in Caenorhabditis elegans upon exposure to toxins evoking different mechanisms of neurotoxicity, including direct oxidative stress and/or excitotoxicity. In rat cortical slices, FA (250 and 500 μM), but not SCAE (~ 270 μM of total polyphenols), prevented the loss of reductive capacity induced by the excitotoxin quinolinic acid (QUIN, 100 μM), the pro-oxidant agent ferrous sulfate (FeSO4, 25 μM), and the dopaminergic pro-oxidant 6-hydroxydopamine (6-OHDA, 100 μM). In wild-type (N2) C. elegans, FA (38 mM) exerted protective effects on decreased survival induced by FeSO4 (15 mM) and 6-OHDA (25 mM), and the motor alterations induced by QUIN (100 mM), FeSO4, and 6-OHDA. In contrast, SCAE (~ 13.5 mM of total polyphenols) evoked protective effects on the decreased survival induced by the three toxic agents, the motor alterations induced by FeSO4, and the reproductive deficit induced by FeSO4. In addition, FA was unable to reverse the decreased survival induced by all these toxins in the skn-1−/− strain (VC1772), which lacks the homolog of mammalian Nrf2, a master antioxidant gene. Altogether, our results suggest that (1) both FA and SCAE afford protection against toxic conditions, (2) not all the effects inherent to SCAE are due to FA, and (3) FA requires the skn-1 pathway to exert its protective effects in C. elegans.

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Acknowledgments

The authors wish to express gratitude to Dr. Pan Chen for his excellent technical contribution.

Funding

MA has been supported in part by the National Institutes of Health grant numbers NIEHS R01ES07331, NIEHS R01ES10563, and NIEHS R01ES020852.

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Author notes

  1. Aline Colonnello and Ilan Kotlar contributed equally to this work.

Authors and Affiliations

  1. Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, 14269, Mexico City, Mexico

    Aline Colonnello, Ilan Kotlar, María Eduarda de Lima & Abel Santamaría

  2. Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

    Aline Colonnello & Ilan Kotlar

  3. Universidade Federal do Pampa, Uruguaiana, RS, Brazil

    María Eduarda de Lima

  4. Laboratorio de Patología Experimental, Instituto Nacional de Neurología y Neurocirugía, 14269, Mexico City, Mexico

    Alma Ortíz-Plata

  5. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

    Rodolfo García-Contreras

  6. Departamento de Bioquimica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Félix Alexandre Antunes Soares

  7. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Michael Aschner

Authors
  1. Aline Colonnello
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  2. Ilan Kotlar
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  3. María Eduarda de Lima
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  4. Alma Ortíz-Plata
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  5. Rodolfo García-Contreras
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  6. Félix Alexandre Antunes Soares
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  7. Michael Aschner
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  8. Abel Santamaría
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Corresponding author

Correspondence to Abel Santamaría.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Colonnello, A., Kotlar, I., de Lima, M.E. et al. Comparing the Effects of Ferulic Acid and Sugarcane Aqueous Extract in In Vitro and In Vivo Neurotoxic Models. Neurotox Res 34, 640–648 (2018). https://doi.org/10.1007/s12640-018-9926-y

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  • DOI: https://doi.org/10.1007/s12640-018-9926-y

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