p-Coumaric acid activates the GABA-A receptor in vitro and is orally anxiolytic in vivo

Phytother Res. 2014 Feb;28(2):207-11. doi: 10.1002/ptr.4968. Epub 2013 Mar 26.


The increasing prevalence and social burden of subclinical anxiety in the western world represents a significant psychosocial and financial cost. Consumers are favouring a more natural and nonpharmacological approach for alleviating the effects of everyday stress and anxiety. The gamma-aminobutyric acid (GABA) receptor is the primary mediator of central inhibitory neurotransmission, and GABA-receptor agonists are well known to convey anxiolytic effects. Using an in vitro screening approach to identify naturally occurring phytochemical GABA agonists, we discovered the plant secondary metabolite p-coumaric acid to have significant GABAergic activity, an effect that could be blocked by co-administration of the specific GABA-receptor antagonist, picrotoxin. Oral administration of p-coumaric acid to rodents induced a significant anxiolytic effect in vivo as measured using the elevated plus paradigm, in line with the effects of oral diazepam. Given that p-coumaric acid is reasonably well absorbed following oral consumption in man and is relatively nontoxic, it may be suitable for the formulation of a safe and effective anxiolytic functional food.

Keywords: GABA; anxiety; diazepam; functional food; p-coumaric acid; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Coumaric Acids / pharmacology*
  • Diazepam / pharmacology
  • GABA Antagonists / pharmacology*
  • Male
  • Motor Activity / drug effects
  • Phytochemicals / pharmacology
  • Picrotoxin / adverse effects
  • Propionates
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism*
  • Synaptic Transmission / drug effects


  • Anti-Anxiety Agents
  • Coumaric Acids
  • GABA Antagonists
  • Phytochemicals
  • Propionates
  • Receptors, GABA-A
  • Picrotoxin
  • p-coumaric acid
  • Diazepam