Chrysin promotes attenuation of depressive-like behavior and hippocampal dysfunction resulting from olfactory bulbectomy in mice.
Chrysin is a natural flavonoid which is found in bee propolis, honey and various plants, and antidepressant-like effect of chrysin in chronically stressed mice was previously demonstrated by our group. In this work, we investigated the action of chrysin treatment (5 or 20 mg/kg) for 14 days in the depressant-like behavior and in the hippocampal dysfunction induced by olfactory bulbectomy (OB), an animal model of agitated depression. Results demonstrated that OB occasioned a depressant-like behavior in the splash test, open field test and forced swimming test. Chrysin administration, similarly to fluoxetine (positive control), promoted the attenuation of these behavioral modifications. OB also caused the elevation of tumor necrosis factor-α, interferon-γ, interleukin-1β, interleukin-6, kynurenine (KYN) levels and indoleamine-2,3-dioxygenase activity, as well as occasioned the decrease of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) levels and increase KYN/tryptophan and 5-hydroxyindoleacetic acid/5-HT ratio in the hippocampus. Chrysin therapy prevented against all these alterations in the hippocampus. In addition, chrysin treatment (20 mg/kg) resulted in the up-regulation of BDNF levels in the control animals, reinforcing our hypothesis that up-regulation of BDNF synthesis play a key role in the antidepressant action of chrysin. In conclusion, this study showed that chrysin, similarly to fluoxetine, is capable of promoting the attenuation of depressant-like behavior and hippocampal dysfunction resulting from OB in mice. These results reinforced the potential of chrysin for the treatment or supplementary treatment of depression, as well as showed that chrysin is also effective with 14 days of therapy in a model of agitated depression.
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
Carlos Borges
CB
Filho
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil. Electronic address: cristianoricardojesse@yahoo.com.br.
Cristiano Ricardo
CR
Jesse
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
Franciele
F
Donato
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
Lucian
L
Del Fabbro
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
Marcelo
M
Gomes de Gomes
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
André Tiago
AT
Rossito Goes
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
Leandro Cattelan
LC
Souza
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
Silvana Peterini
SP
Boeira
D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology*; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery*; D012701:Serotonin / Q000378:metabolism
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D005419:Flavonoids; D005473:Fluoxetine; D012701:Serotonin; C043561:chrysin
Antidepressant-like effect; Cytokines; Flavonoid; Inflammation; Olfactory bulbectomy