title: Anxiolytic activity and active principles of Piper amalago (Piperaceae), a medicinal plant used by the Q'eqchi' Maya to treat susto, a culture-bound illness.
abstract: BACKGROUND
  The medicinal plant, Piper amalago L. (Piperaceae), is used traditionally by Q'eqchi' Maya healers for the treatment of "susto" a culture-bound syndrome. Previous research suggests that susto symptoms may be a manifestation of anxiety. The objectives were to characterize the effect of ethanolic extract of P. amalago in behavioral assays of anxiety at doses representative of traditional use and to isolate active principles.
  
  
  METHODS
  Rats treated orally with low dose ethanolic extracts of P. amalago leaves (8-75mg/kg) were tested in several behavioral paradigms including the elevated plus maze (EPM), social interaction (SI), and conditioned emotional response (CER) tests, and compared to diazepam, a positive control. The active anxiolytic principle was isolated by bioassay guided isolation using an in vitro GABAA competitive binding assay.
  
  
  RESULTS
  Extracts had significant anxiolytic activity in all behavioral tests, with the strongest activity in the SI and the CER paradigms. In an in vitro GABAA competitive binding assay, a 66.5µg/mL concentration of P. amalago ethanol extract displaced 50% of the GABAA-BZD receptor ligand [(3)H]-Flunitrazepam. Bioassay-guided fractionation identified a furofuran lignan, a molecule with structural similarity to yangambin, with high affinity for the GABAA-BZD receptor as the principle bioactive.
  
  
  CONCLUSIONS
  The results suggest that the ethnobotanical use of this plant may have a pharmacological basis in its anxiolytic activity, as demonstrated in animal behaviour tests.
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada.
authors.forename: M
authors.initials: M
authors.lastname: Mullally
authors.affiliation: University of Ottawa Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada; School of Psychology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada.
authors.forename: C
authors.initials: C
authors.lastname: Cayer
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada.
authors.forename: A
authors.initials: A
authors.lastname: Muhammad
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada.
authors.forename: B
authors.initials: B
authors.lastname: Walshe-Roussel
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada.
authors.forename: F
authors.initials: F
authors.lastname: Ahmed
authors.affiliation: JVR Herbarium, Campus Omar Dengo, Universidad Nacional, Heredia, Costa Rica.
authors.forename: P E
authors.initials: PE
authors.lastname: Sanchez-Vindas
authors.affiliation: JVR Herbarium, Campus Omar Dengo, Universidad Nacional, Heredia, Costa Rica.
authors.forename: M
authors.initials: M
authors.lastname: Otarola Rojas
authors.affiliation: University of Ottawa Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada; School of Psychology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Merali
authors.affiliation: Belize Indigenous Training Institute, Punta Gorda, Belize.
authors.forename: V
authors.initials: V
authors.lastname: Cal
authors.affiliation: Department of Chemistry, University of Ottawa, ON, K1N 6N5 Canada.
authors.forename: T
authors.initials: T
authors.lastname: Durst
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada.
authors.forename: V L
authors.initials: VL
authors.lastname: Trudeau
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5 Canada. Electronic address: jarnason@science.uottawa.ca.
authors.forename: J T
authors.initials: JT
authors.lastname: Arnason
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D006801:Humans; D017705:Lignans / Q000737:chemistry; D008297:Male; D008519:Medicine, Traditional; D015394:Molecular Structure; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014151:Anti-Anxiety Agents; D017705:Lignans; D010936:Plant Extracts
keywords: Anxiety; GABA(A)-BZD receptor binding; Piperaceae; Susto