title: Pharmacological evaluation of the anxiolytic-like effects of Lippia graveolens and bioactive compounds.
abstract: BACKGROUND
  Lippia species (Verbenaceae) are widely used in Latin America and Africa as folk medicine for their tranquilizing properties.
  
  
  OBJECTIVE
  To evaluate the anxiolytic-like effects and safety of Lippia graveolens Kunth. by exploring its aqueous and organic leaf extracts and identifying the responsible chemical constituents.
  
  
  METHODS
  Aqueous and organic extracts (hexane, ethyl acetate and methanol) were pharmacologically evaluated at several doses. Chemical constituents were identified using MS, NMR and GC-MS analysis. The isolated compounds (3 mg/kg, i.p.), extracts (1, 3, 10 and 30 mg/kg, i.p.), and the reference drug diazepam (0.1 mg/kg, i.p.) were assessed in CD-1 mice using experimental behavioural models: open-field, cylinder, hole-board, plus-maze and sodium pentobarbital-induced hypnosis, as well as their acute toxicity (LD50).
  
  
  RESULTS
  After administration of the extracts and bioactive compounds, a significant anxiolytic-like response from 1 mg/kg, i.p. was observed, resembling the effect of diazepam. Major presence of thymol (33.40%) was observed in the hexane extract; whereas for the first time in this species a p-cymene + thymol mixture (9.78%), naringenin (0.18%) and cirsimaritin (1.16%) were obtained as bioactive constituents of the ethyl acetate crude extract. Acute toxicity was calculated to be LD50= 1000 mg/kg for the crude hexane extract, lower in comparison to the other extracts analyzed (LD50> 2000 mg/kg).
  
  
  CONCLUSIONS
  Our results suggest that L. graveolens exerts anxiolytic-like activity involving many kinds of constituents, mainly of the terpenoid and flavonoid nature. These results reinforce the potential use of this species in the therapy of anxiety.
authors.affiliation: a Laboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias , Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz , Mexico City , Mexico.
authors.forename: María Eva
authors.initials: ME
authors.lastname: González-Trujano
authors.affiliation: b Laboratorio de Fitoquímica, Departamento de Ecología y Recursos Naturales. Facultad de Ciencias , Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán , Mexico city , Mexico.
authors.forename: Laura Yunuen
authors.initials: LY
authors.lastname: Hernández-Sánchez
authors.affiliation: b Laboratorio de Fitoquímica, Departamento de Ecología y Recursos Naturales. Facultad de Ciencias , Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán , Mexico city , Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Muñoz Ocotero
authors.affiliation: c Centro Conjunto de Investigación en Química Sustentable, Toluca, Estado de México, México. Instituto de Química, Universidad Nacional Autónoma de México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Dorazco-González
authors.affiliation: b Laboratorio de Fitoquímica, Departamento de Ecología y Recursos Naturales. Facultad de Ciencias , Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán , Mexico city , Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Guevara Fefer
authors.affiliation: b Laboratorio de Fitoquímica, Departamento de Ecología y Recursos Naturales. Facultad de Ciencias , Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán , Mexico city , Mexico.
authors.forename: Eva
authors.initials: E
authors.lastname: Aguirre-Hernández
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001007:Anxiety / Q000517:prevention & control* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D007928:Lethal Dose 50; D032411:Lippia / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D064209:Phytochemicals / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal; D012890:Sleep / Q000187:drug effects; D012997:Solvents / Q000737:chemistry
chemical_list: D014151:Anti-Anxiety Agents; D064209:Phytochemicals; D010936:Plant Extracts; D012997:Solvents; D003975:Diazepam
keywords: Anxiety; Mexican traditional medicine; cirsimaritin; naringenin; terpenoid; verbenaceae