Neurochemical factors associated with the antidepressant-like effect of flavonoid chrysin in chronically stressed mice.
Chrysin is a flavonoid which is found in bee propolis, honey and various plants. Antidepressant-like effect of chrysin in chronically stressed mice was previously demonstrated by our group. Conversely, neurochemical factors associated with this effect require further investigations. Thus, we investigated the possible involvement of pro-inflammatory cytokines, kynurenine pathway (KP), 5-hydroxytryptamine (5-HT) metabolism and caspases activities in the effect of chrysin in mice exposed to unpredictable chronic stress (UCS). UCS applied for 28 days induced a depressive-like behavior, characterized by decrease in the time of grooming in the splash test and by increase in the immobility time in the tail suspension test. Oral treatment with chrysin (5 or 20mg/kg, 28 days), similarly to fluoxetine (10mg/kg, positive control), culminated in the prevention of these alterations. UCS elevated plasma levels of corticotropin-releasing hormone and adrenocorticotropic hormone, as well the tumor necrosis factor-α, interleukin-1β, interleukin-6 and kynurenine levels in the prefrontal cortex (PFC) and hippocampus (HP). UCS induced the decrease in the 5-HT levels in the HP and the increase in the indoleamine-2,3-dioxygenase, caspase 3 and 9 activities in the PFC and HP. Treatment with chrysin, similarly to fluoxetine, promoted the attenuation of these alterations occasioned by UCS. These results corroborated with the antidepressant potential of chrysin in the treatment of psychiatric diseases. Furthermore, this work indicated the association of pro-inflammatory cytokines synthesis, KP, 5-HT metabolism and caspases activities with the action exercised by chrysin in mice exposed to UCS.
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 Gomes
MG
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 Rossito
ATR
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.
Renata
R
Giacomeli
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
Michelle
M
Antunes
Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário, s/n, 96160-000 Capão do Leão, RS, Brazil.
Cristiane
C
Luchese
Universidade Regional Integrada, Campus Erechim, CEP 99700-000 RS, Brazil.
Silvane Souza
SS
Roman
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
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D051379:Mice; D009448:Neurochemistry; D018019:Receptors, Corticotropin-Releasing Hormone / Q000097:blood; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
D000928:Antidepressive Agents; D016207:Cytokines; D005419:Flavonoids; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018019:Receptors, Corticotropin-Releasing Hormone; D012701:Serotonin; D007737:Kynurenine; C043561:chrysin; D014364:Tryptophan; D000324:Adrenocorticotropic Hormone; D020169:Caspases
Antidepressant-like; Chronic stress; Depression; Flavonoid