Uliginosin B, a phloroglucinol derivative from Hypericum polyanthemum: A promising new molecular pattern for the development of antidepressant drugs

• Published in: Behavioural brain research 2012-03, Vol.228 (1), p.66-73
• Main Authors: Stein, Ana C., Viana, Alice F., Müller, Liz G., Nunes, Jéssica M., Stolz, Eveline D., Do Rego, Jean-Claude, Costentin, Jean, von Poser, Gilsane L., Rates, Stela M.K.
• Format: Article
• Language: English
• Subjects: Animals; Antidepressant; Antidepressive Agents - isolation & purification; Antidepressive Agents - pharmacology; Benzazepines - pharmacology; Biogenic Monoamines - metabolism; Bupropion - pharmacology; Drug Evaluation, Preclinical - methods; Drug Evaluation, Preclinical - psychology; Enzyme Inhibitors - pharmacology; Fenclonine - pharmacology; Fluoxetine - pharmacology; Forced swimming test; Hypericum - chemistry; Hypericum polyanthemum; Imipramine - pharmacology; Immobility Response, Tonic - drug effects; Locomotion - drug effects; Male; Mice; Mice, Inbred Strains; Monoaminergic neurotransmission; Phloroglucinol - analogs & derivatives; Phloroglucinol - antagonists & inhibitors; Phloroglucinol - isolation & purification; Phloroglucinol - pharmacology; Plant Extracts - chemistry; Plant Extracts - pharmacology; Prazosin - pharmacology; Rats; Rats, Wistar; Receptors, Catecholamine - antagonists & inhibitors; Sulpiride; Uliginosin B; Vesicular Monoamine Transport Proteins - metabolism; Yohimbine - pharmacology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2011.11.031

► H. polyanthemum and uliginosin B cause antidepressant effect in forced swimming test. ► H. polyanthemum and uliginosin B potentiate antidepressants antiimobility activity in forced swimming test. ► Uliginosin B antidepressant-like effect depends on monoaminergic neurotransmission. ► Uliginosin B inhibits monoamines uptake without binding to their transporters. ► Uliginosin B provides a new molecular pattern to develop innovative antidepressants. 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 (1 mg/kg, i.p., α1-adrenoceptor antagonist), yohimbine (1 mg/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 (IC 50 = 90 ± 38 nM), serotonin (IC 50 = 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.