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

Neurotox Res. 2018 Oct;34(3):640-648. doi: 10.1007/s12640-018-9926-y. Epub 2018 Jun 15.

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.

Keywords: Antioxidant defense; C. elegans; Ferulic acid; Neurotoxic models; Protective effects; Rat cortical slices; Sugarcane.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Birth Rate
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Coumaric Acids / therapeutic use*
  • Disease Models, Animal
  • Ferrous Compounds / toxicity
  • In Vitro Techniques
  • Iron / metabolism
  • Locomotion / drug effects
  • Male
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / physiopathology
  • Oxidopamine / toxicity
  • Plant Extracts / chemistry
  • Plant Extracts / therapeutic use*
  • Quinolinic Acid / toxicity
  • Rats
  • Rats, Wistar
  • Saccharum / chemistry*

Substances

  • Caenorhabditis elegans Proteins
  • Coumaric Acids
  • Ferrous Compounds
  • Plant Extracts
  • ferrous sulfate
  • Oxidopamine
  • ferulic acid
  • Iron
  • Quinolinic Acid