Anxiolytic-like, Stimulant and Neuroprotective Effects of Ilex Paraguariensis Extracts in Mice

Neuroscience. 2015 Apr 30;292:13-21. doi: 10.1016/j.neuroscience.2015.02.004. Epub 2015 Feb 11.


Yerba-mate (Ilex paraguariensis St. Hil.) is the most used beverage in Latin America with approximately 426 thousand of tons consumed per year. Considering the broad use of this plant, we aimed to investigate the anxiety-like and stimulant activity of both the hydroethanolic (HE) and aqueous (AE) extracts from leaves of I. paraguariensis. Swiss mice were treated with I. paraguariensis HE or AE chronically or acutely, respectively, followed by evaluation in the elevated plus-maze (EPM; anxiety-like paradigm), open field (OF; locomotor activity) or the step-down avoidance task (memory assessment). Following behavioral protocols the brains were collected for evaluation of acetylcholinesterase (AChE) activity ex vivo. Chronic treatment with HE induced an anxiolytic-like effect and increased motor activity besides augmented AChE activity. Additionally, acute treatment with AE prevented the scopolamine-induced memory deficit in the step-down avoidance task. Overall, our results indicate the importance of the I. paraguariensis-induced CNS effects, since it is a widely used nutraceutical. We have reported anxiolytic, stimulant and neuroprotective effects for this plant species. These effects are potentially modulated by the cholinergic system as well as by caffeine.

Keywords: Ilex paraguariensis; anxiety; caffeine; memory; stimulant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety / drug therapy
  • Avoidance Learning / drug effects
  • Brain / drug effects
  • Brain / enzymology
  • Caffeine / chemistry
  • Caffeine / pharmacology
  • Central Nervous System Stimulants / chemistry
  • Central Nervous System Stimulants / pharmacology*
  • Cholinergic Agents / chemistry
  • Cholinergic Agents / pharmacology
  • Exploratory Behavior / drug effects
  • Ilex paraguariensis* / chemistry
  • Male
  • Memory Disorders / prevention & control
  • Mice
  • Motor Activity / drug effects
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Phototherapy
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves* / chemistry
  • Scopolamine


  • Anti-Anxiety Agents
  • Central Nervous System Stimulants
  • Cholinergic Agents
  • Neuroprotective Agents
  • Plant Extracts
  • Caffeine
  • Scopolamine
  • Acetylcholinesterase