title: Uliginosin B, a phloroglucinol derivative from Hypericum polyanthemum: a promising new molecular pattern for the development of antidepressant drugs.
abstract: In this study we have demonstrated that cyclohexane extract of Hypericum polyanthemum (POL) and its main phloroglucinol derivative uliginosin B (ULI) present antidepressant-like activity in rodent forced swimming test (FST). The involvement of monoaminergic neurotransmission on the antidepressant-like activity of ULI was evaluated in vivo and in vitro. POL 90 mg/kg (p.o.) and ULI 10 mg/kg (p.o.) reduced the immobility time in the mice FST without altering locomotion activity in the open-field test. The combination of sub-effective doses of POL (45 mg/kg, p.o.) and ULI (5 mg/kg, p.o.) with sub-effective doses of imipramine (10 mg/kg, p.o.), bupropion (3 mg/kg, p.o.) and fluoxetine (15 mg/kg, p.o.) induced a significant reduction on immobility time in FST. The pretreatment with SCH 23390 (15 μg/kg, s.c., dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., α2-adrenoceptor antagonist) and pCPA (100 mg/kg/day, i.p., p-chlorophenilalanine methyl ester, inhibitor of serotonin synthesis, for four consecutive days) before ULI administration (10 mg/kg, p.o.) significantly prevented the anti-immobility effect in FST. ULI was able to inhibit synaptosomal uptake of dopamine (IC50 = 90 ± 38 nM), serotonin (IC50 = 252 ± 13 nM) and noradrenaline (280 ± 48 nM), but it did not bind to any of the monoamine transporters. These data firstly demonstrated the antidepressant-like effect of POL and ULI, which depends on the activation of the monoaminergic neurotransmission in a different manner from the most antidepressants.
authors.affiliation: Graduate Studies Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Stein
authors.forename: Alice F
authors.initials: AF
authors.lastname: Viana
authors.forename: Liz G
authors.initials: LG
authors.lastname: Müller
authors.forename: Jéssica M
authors.initials: JM
authors.lastname: Nunes
authors.forename: Eveline D
authors.initials: ED
authors.lastname: Stolz
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Do Rego
authors.forename: Jean
authors.initials: J
authors.lastname: Costentin
authors.forename: Gilsane L
authors.initials: GL
authors.lastname: von Poser
authors.forename: Stela M K
authors.initials: SM
authors.lastname: Rates
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism; D016642:Bupropion / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000523:psychology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D020902:Hypericum / Q000737:chemistry*; D007099:Imipramine / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017983:Receptors, Catecholamine / Q000037:antagonists & inhibitors; D013469:Sulpiride; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D001552:Benzazepines; D015306:Biogenic Monoamines; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D017983:Receptors, Catecholamine; C534628:SCH 23390; D050493:Vesicular Monoamine Transport Proteins; D005473:Fluoxetine; D016642:Bupropion; D015016:Yohimbine; D013469:Sulpiride; D010696:Phloroglucinol; D007099:Imipramine; C547933:uliginosin B; D010134:Fenclonine; D011224:Prazosin