title: Plurality of anxiety and depression alteration mechanism by oleanolic acid.
abstract: Our study sought to evaluate the anxiolytic and antidepressant activities of oleanolic acid as well as the neural mechanisms involved. Animal models such as barbiturate sleep-induction, light-dark box, elevated plus maze, forced swimming test, tail suspension test and open field test were conducted. Male Albino Swiss mice were treated orally with vehicle 10 mL/kg, fluoxetine 20 mg/kg, imipramine 15 mg/kg, diazepam 1 mg/kg or oleanolic acid 5-40 mg/kg. Pretreatment (intraperitoneal) of animals with pentylenetetrazole (PTZ) 20 mg/kg, 1-(2-methoxyphenyl)-4-[4- (2-phthalimido) butyl]piperazine hydrobromide (NAN-190) 0.5 mg/kg, p-chlorophenylalanine methyl ester (PCPA) 100 mg/kg or α-methyl-p-tyrosine (AMPT) 100 mg/kg, WAY100635 (WAY) 0.3 mg/kg, prazosin (PRAZ) 1 mg/kg, yohimbine 2 mg/kg as well as monoamine oxidase assay and hippocampal brain-derived neurotrophic factor (BDNF) quantification were carried out. Oleanolic acid potentiated the hypnotic effect of barbiturate and demonstrated an anxiolytic effect in both the light-dark box and elevated plus maze. This effect was not reversed by PTZ. Acute and/or chronic oral treatment of mice with oleanolic acid (5-20 mg/kg) elicited an antidepressant effect in the forced swimming test and the tail suspension test without interfering with the locomotor activity. The antidepressant effect of oleanolic acid was attenuated by NAN-190, AMPT, PCPA, WAY and PRAZ. Although monoamine oxidase activity remained unaltered by oleanolic acid, chronic administration of oleanolic acid augmented hippocampal BDNF level. These findings demonstrate multiple mechanisms of the anxiolytic and antidepressant effect of oleanolic acid.
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia-GO, Brazil olulolo@yahoo.com.
authors.forename: James O
authors.initials: JO
authors.lastname: Fajemiroye
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia-GO, Brazil.
authors.forename: Pablinny M
authors.initials: PM
authors.lastname: Galdino
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia-GO, Brazil.
authors.forename: Iziara F
authors.initials: IF
authors.lastname: Florentino
authors.affiliation: Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fabio F
authors.initials: FF
authors.lastname: Da Rocha
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia-GO, Brazil.
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Ghedini
authors.affiliation: Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
authors.forename: Prabhakar R
authors.initials: PR
authors.lastname: Polepally
authors.affiliation: Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Zjawiony
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia-GO, Brazil.
authors.forename: Elson A
authors.initials: EA
authors.lastname: Costa
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000031:analogs & derivatives / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009828:Oleanolic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D010879:Piperazines; D011725:Pyridines; D005473:Fluoxetine; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C020261:4-chlorophenylalanine methyl ester; D019805:alpha-Methyltyrosine; D009828:Oleanolic Acid; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D008995:Monoamine Oxidase; D007099:Imipramine; D003975:Diazepam; D010134:Fenclonine; D010433:Pentylenetetrazole
keywords: Oleanolic acid; antidepressant; anxiolytic; metabolic enzymes; monoamine; neurotrophic factor