title: Interactions of a standardized flavonoid fraction from Tilia americana with Serotoninergic drugs in elevated plus maze.
abstract: BACKGROUND
  Tilia americana var. mexicana (Schltdl) Hardin (Tiliaceae) aerial parts (bracts and flowers) are used in the traditional Mexican medicine to treat nervous disorders, as sedative and to treat insomnia. A fraction of this species called FC1 (organic fraction from this plant) was proposed, described as anxiolytic and characterized by the presence of flavonoids. In the present work, this fraction was standardized, and its interaction with different serotonergic drugs was tested. We used the elevated plus maze model as anxiety test and the open field test so as to observe a possible effect on mice׳s motor behavior.
  
  
  METHODS
  HPLC technique was used to quantify the flavonoids contained in a fraction called F1C. Different doses of F1C were administered to ICR mice (12.5, 25, 37.5 and 50mg/kg, oral pathway) then they were exposed to elevated plus maze or open field test. After, each dose of F1C fraction was co-administered with different drugs, in order to evaluate the animal׳s behavior: DOI agonist (2.0mg/kg) and KET antagonist (0.03mg/kg) of 5-HT2A receptors; 8-OH-DPAT (0.1mg/kg) selective agonist and WAY100635 (0.5mg/kg) antagonist of 5HT1 receptors.
  
  
  RESULTS
  The HPLC quantitative analysis revealed the F1C composition (mg/g of extract): tiliroside (28.56), glucoside of quercetin (16.25), quercitrin (7.96), rutin (3.93), Kaempferol (2.83). The Emax for F1C curve was 80.6% for time to open arms with an ED50 of 15.09 mg/kg. The combination of F1C with DOI gives a significant increase of the F1C anxiolytic effect (Emax=111% and ED50=13.51 mg/kg), while KET blocks it completely (Emax=12.25% and ED50=2.4 mg/kg). The administration of F1C with 8-OH-DPAT does not generate significant changes on the time to open arms, although it does induce a decrement in F1C potency (Emax=83.3% and ED50=33.3mg/kg). When F1C and WAY-100365 are combined, the anxiolytic activity of the fraction decreases (Emax=33.3% and ED50=102.10mg/kg).
  
  
  CONCLUSIONS
  The medicinal use attributed to Tilia americana for their effect on central nervous system, could be in part in the flavonoid fraction (F1C) with anxiolytic activity which is dose dependent, and has the ability to interact with the serotonergic system. It is necessary to advance in the study of the mechanism of action, using other techniques such in vitro analysis.
authors: Centro de Investigación Biomédica del Sur (CIBIS), Instituto Mexicano del Seguro Social (IMSS), Argentina No. 1, Col. Centro, C.P. 62790 Xochitepec, Morelos, Mexico; Programa de Doctorado de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina C.P. 09340, Iztapalapa, México D.F., Mexico; Departamento de Farmacología, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina C.P. 09340, Iztapalapa, México D.F., Mexico. Electronic address: macarnogmer@hotmail.com.
authors: M C
authors: MC
authors: Noguerón-Merino
authors: Centro de Investigación Biomédica del Sur (CIBIS), Instituto Mexicano del Seguro Social (IMSS), Argentina No. 1, Col. Centro, C.P. 62790 Xochitepec, Morelos, Mexico. Electronic address: enriqueferrer_mx@yahoo.com.
authors: E
authors: E
authors: Jiménez-Ferrer
authors: Departamento de Farmacología, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina C.P. 09340, Iztapalapa, México D.F., Mexico. Electronic address: rrr@xanum.uam.mx.
authors: R
authors: R
authors: Román-Ramos
authors: Centro de Investigación Biomédica del Sur (CIBIS), Instituto Mexicano del Seguro Social (IMSS), Argentina No. 1, Col. Centro, C.P. 62790 Xochitepec, Morelos, Mexico. Electronic address: azamilpa_2000@yahoo.com.mx.
authors: A
authors: A
authors: Zamilpa
authors: Centro de Investigación Biomédica del Sur (CIBIS), Instituto Mexicano del Seguro Social (IMSS), Argentina No. 1, Col. Centro, C.P. 62790 Xochitepec, Morelos, Mexico. Electronic address: jtortora2@yahoo.es.
authors: J
authors: J
authors: Tortoriello
authors: Centro de Investigación Biomédica del Sur (CIBIS), Instituto Mexicano del Seguro Social (IMSS), Argentina No. 1, Col. Centro, C.P. 62790 Xochitepec, Morelos, Mexico. Electronic address: cibis_herj@yahoo.com.mx.
authors: M
authors: M
authors: Herrera-Ruiz
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000032:analysis / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology*; D032384:Tilia
chemical_list: D014151:Anti-Anxiety Agents; D005419:Flavonoids; D010936:Plant Extracts; D018490:Serotonin Agents
keywords: 5-HT1A; 5-HT2-A; Anxiety; Elevated plus-maze; Flavonols; Tilia americana