Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 74, Issue 1, Pages 13-21Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgab128
Keywords
ursolic acid; heme oxygenase-1; antidepressant; tail suspension test; cobalt protoporphyrin; zinc protoporphyrin
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [310113/2017-2]
- Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina (FAPESC)
- CNPq Research Productivity Fellowship
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The study discovered the crucial role of HO-1 in mediating the antidepressant-like effects of UA, and revealed a synergistic antidepressant effect when UA was combined with CoPP. Interestingly, fluoxetine did not show a significant correlation with the activity of HO-1.
Objectives This study investigated the involvement of heme oxygenase-1 (HO-1) in the antidepressant-like effects of ursolic acid (UA), a plant-derived compound with neuroprotective and antidepressant-like properties. Methods Mice received intracerebroventricular injections of zinc protoporphyrin IX (ZnPP) or cobalt protoporphyrin IX (CoPP) to inhibit or induce HO-1, respectively, together with effective (0.1 mg/kg, p.o.) or sub-effective (0.01 mg/kg, p.o.) doses of UA or fluoxetine (10 mg/kg, p.o.). Immobility time was assessed using the tail suspension test (TST) and the ambulatory behaviour with the open field test. HO-1 immunocontent was evaluated in mice hippocampus and prefrontal cortex. Key findings ZnPP prevented the anti-immobility effects of UA and fluoxetine. Combined treatment with a sub-effective dose of CoPP and UA synergistically exerted antidepressant-like effects in the TST. Acute administration of UA or CoPP, but not fluoxetine, increased the HO-1 immunocontent in the hippocampus. None of the treatments altered the HO-1 immunocontent in the prefrontal cortex. Conclusions In conclusion, this work shows that increased hippocampal HO-1 content and activity mediate the antidepressant-like effect of UA in the TST.
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