title: p-Coumaric acid activates the GABA-A receptor in vitro and is orally anxiolytic in vivo.
abstract: 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.
authors.affiliation: The New Zealand Institute for Plant and Food Research, 120 Mt Albert Rd, Sandringham, Auckland, 1142, New Zealand.
authors.forename: Arjan
authors.initials: A
authors.lastname: Scheepens
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Bisson
authors.forename: Margot
authors.initials: M
authors.lastname: Skinner
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003373:Coumaric Acids / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D064209:Phytochemicals / Q000494:pharmacology; D010852:Picrotoxin / Q000009:adverse effects; D011422:Propionates; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D003373:Coumaric Acids; D003975:Diazepam; D018756:GABA Antagonists; D064209:Phytochemicals; D010852:Picrotoxin; D011422:Propionates; D011963:Receptors, GABA-A; C495469:p-coumaric acid
keywords: GABA; anxiety; diazepam; functional food; p-coumaric acid; stress