title: Oleanolic acid acrylate elicits antidepressant-like effect mediated by 5-HT1A receptor.
abstract: The development of new drugs for the treatment of depression is strategic to achieving clinical needs of patients. This study evaluates antidepressant-like effect and neural mechanisms of four oleanolic acid derivatives i.e. acrylate (D1), methacrylate (D2), methyl fumarate (D3) and ethyl fumarate (D4). All derivatives were obtained by simple one-step esterification of oleanolic acid prior to pharmacological screening in the forced swimming (FS) and open field (OF) tests. Pharmacological tools like α-methyl-p-tyrosine (AMPT, catecholamine depletor), p-chlorophenylalanine (serotonin depletor), prazosin (PRAZ, selective α1-receptor antagonist), WAY-100635 (selective serotonin 5-HT1A receptor antagonist) as well as monoamine oxidase (MAO) and functional binding assays were conducted to investigate possible neural mechanisms. In the FS test, D1 showed the most promising antidepressant-like effect without eliciting locomotor incoordination. Unlike group of mice pretreated with AMPT 100 mg/kg, PCPA 100 mg/kg or PRAZ 1 mg/kg, the effect of D1 was attenuated by WAY-100635 0.3 mg/kg pretreatment. D1 demonstrated moderate inhibition of MAO-A (IC50 = 48.848 ± 1.935 μM), potency (pEC50 = 6.1 ± 0.1) and intrinsic activity (E max = 26 ± 2.0%) on 5-HT1A receptor. In conclusion, our findings showed antidepressant-like effect of D1 and possible involvement of 5-HT1A receptor.
authors.affiliation: Department of Pharmacology, Federal University of Goias, Campus Samambaia, 74001-970, Goiania, GO, Brazil.
authors.forename: James O
authors.initials: JO
authors.lastname: Fajemiroye
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, P.O. Box 1848, University, MS 38677, USA.
authors.forename: Prabhakar R
authors.initials: PR
authors.lastname: Polepally
authors.affiliation: National Center for Natural Products Research, University of Mississippi, P.O. Box 1848, University, MS 38677, USA.
authors.forename: Narayan D
authors.initials: ND
authors.lastname: Chaurasiya
authors.affiliation: 1] National Center for Natural Products Research, University of Mississippi, P.O. Box 1848, University, MS 38677, USA [2] Department of BioMolecular Sciences, Division of Pharmacology School of Pharmacy, University of Mississippi, P.O. Box 1848, University, MS 38677, USA.
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, P.O. Box 1848, University, MS 38677, USA.
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Zjawiony
authors.affiliation: Department of Pharmacology, Federal University of Goias, Campus Samambaia, 74001-970, Goiania, GO, Brazil.
authors.forename: Elson A
authors.initials: EA
authors.lastname: Costa
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D013550:Swimming
chemical_list: D000179:Acrylates; D044282:Receptor, Serotonin, 5-HT1A; D009828:Oleanolic Acid