Uliginosin B, a natural phloroglucinol derivative, presents a multimediated antinociceptive effect in mice

• Published in: Journal of pharmacy and pharmacology 2014-12, Vol.66 (12), p.1774-1785
• Main Authors: Stolz, Eveline Dischkaln, Hasse, Diego Rafael, von Poser, Gilsane Lino, Rates, Stela M. K.
• Format: Article
• Language: English
• Subjects: Analgesics - isolation & purification; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; antinociceptive; Behavior, Animal - drug effects; Biogenic Monoamines - metabolism; glutamatergic neurotransmission; Glutamic Acid - metabolism; Hypericum; Hypericum - chemistry; Hypericum; monoaminergic neurotransmission; Male; Mice, Inbred Strains; monoaminergic neurotransmission; Pain - drug therapy; Pain - metabolism; Pain - psychology; Pain Measurement; Pain Threshold - drug effects; phloroglucinol; Phloroglucinol - analogs & derivatives; Phloroglucinol - isolation & purification; Phloroglucinol - pharmacology; Phloroglucinol - therapeutic use; Plant Components, Aerial - chemistry; Plant Extracts - chemistry; Rodents; Synaptic Transmission - drug effects
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12307

Objective Investigate the involvement of monoaminergic and glutamatergic systems on the antinociceptive and ataxic effects of uliginosin B, which we have already demonstrated to be a promising molecular scaffold to develop new analgesic drugs. Methods Uliginosin B was obtained from hexane extract of aerial parts of Hypericum polyanthemum by chromatographic methods. Uliginosin B antinociceptive and motor coordination effects were evaluated in mice by using hot‐plate (15 and 90 mg/kg, i.p.) and rotarod (90 mg/kg, i.p.) tests, respectively. The mechanism of action was investigated through pretreatments with prazosin 1 mg/kg intraperitoneal (α1 receptor antagonist), yohimbine 5 mg/kg intraperitoneal (α2 receptor antagonist), pCPA 300 mg/kg intraperitoneal (serotonin synthesis inhibitor) and MK‐801 0.25 mg/kg intraperitoneal (N‐methyl‐D‐aspartic acid receptor antagonist). Key findings The antinociceptive effect of uliginosin B (15 and 90 mg/kg, i.p.) was reduced significantly by pCPA and MK‐801. Prazosin and yohimbine improved the antinociceptive effect of the highest dose (90 mg/kg, i.p.) of uliginosin B only. The ataxic effect of uliginosin B (90 mg/kg, i.p.) was completely prevented by pretreatment with pCPA or MK‐801, but it was unaffected by pretreatment with prazosin or yohimbine. Conclusion These data confirm the contribution of monoaminergic neurotransmission as well as provide the first evidence of glutamatergic neurotransmission contribution to the uliginosin B effects.