Neurochemical factors associated with the antidepressant-like effect of flavonoid chrysin in chronically stressed mice

Abstract

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.

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

“…, 28 days), similar to antidepressant fluoxetine (10 mg/kg, p.o. , 28 days), increases serotonin concentration and reduces the indoleamine-2,3-dioxygenase and caspases 3 and 9 activities in the prefrontal cortex and hippocampus in C57B/6J mice subjected to CUMS, which was associated with the antidepressant-like effect detected in the tail suspension test [ 118 ], with the participation of BDNF. Similarly, the administration of 20 and 40 mg/kg of the flavonoid orientin for 21 days also produced antidepressant-like effects in mice that were subjected to CUMS, and this effect was associated with the activation of BDNF and an increase in serotonin and norepinephrine concentration in the hippocampus and cerebral cortex [ 40 ].…”

Antidepressant Flavonoids and Their Relationship with Oxidative Stress

“…In another study done by the same research group members [ 46 ], they showed that the treatment with chrysin caused the attenuation of depressive-like behavior and hippocampal changes in olfactory bulbectomized mice, reinforcing that BDNF plays an important role in the antidepressant effect of this flavonoid. Further, Filho et al [ 47 ] likewise analyzed the neurochemical parameters correlated with the antidepressant property of chrysin in mice exposed to unpredictable chronic stress. The authors suggested an association existing between the antidepressant-like action of chrysin and the proinflammatory cytokines synthesis, 5-hydroxytryptamine metabolism, kynurenine pathway, and caspases activities.…”

Blueberry Phenolics Reduce Gastrointestinal Infection of Patients with Cerebral Venous Thrombosis by Improving Depressant-Induced Autoimmune Disorder via miR-155-Mediated Brain-Derived Neurotrophic Factor

“…Unpredictable chronic stress in an animal model also involves synthesis of pro-inflammatory cytokines, kynurenine pathway (KP), 5-hydroxytryptamine metabolism and caspase activities. Phenolics can reduce the levels or metabolism of these molecules and their activities (Filho et al, 2016 ). On the other hand, phenolics can prevent age-associated memory loss by scavenging free radicals and modulating BDNF levels (Souza et al, 2015 ).…”