Saffron carotenoids reversed the UCMS-induced depression and anxiety in rats: Behavioral and biochemical parameters, and hippocampal BDNF/ERK/CREB and NR2B signaling markers.
Rats
Animals
Depression
/ drug therapy
Crocus
/ chemistry
Brain-Derived Neurotrophic Factor
/ metabolism
Serotonin Plasma Membrane Transport Proteins
/ metabolism
Corticosterone
Fluoxetine
/ pharmacology
Receptors, N-Methyl-D-Aspartate
/ metabolism
Serotonin
/ metabolism
Carotenoids
/ pharmacology
Hippocampus
/ metabolism
Anxiety
/ drug therapy
Corticosterone
Crocetin
Crocin
Fluoxetine
Serotonin
Signaling Pathway
Unpredictable Chronic Mild Stress
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
29
03
2023
revised:
13
06
2023
accepted:
18
07
2023
medline:
31
8
2023
pubmed:
29
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
Depression is a debilitating condition that affects the mind and the individual's body. The improving effects of saffron on depression and anxiety have long been discussed, with limited information about the molecular mechanism of action. Investigating the effect of saffron carotenoids, Crocin and Crocetin, on depression and anxiety in rats by emphasizing some signaling pathways involved. Depression and anxiety were induced in rats via unpredictable chronic mild stress (UCMS). Then different rat groups were treated with Crocin, Crocetin, Fluoxetine, and vehicle. Behavioral tests were done before and after treatment. The serum Serotonin and Corticosterone and the expression of some hippocampal signaling proteins were studied. Furthermore, bioinformatics tools were used to predict the interactions of Crocin/ Crocetin with the Serotonin transporter and NMDA receptor subunit NR2B. Then, the patch-clamp was used to study the interaction of Crocetin with the NMDA receptor. Various behavioral tests confirmed the induction of depression and the improvement of depression by these natural carotenoids. In addition, Crocin/ Crocetin significantly increased the decreased serum Serotonin and reduced the increased serum Corticosterone in the depressed groups. They also increased or caused a trend of increase in the CREB, ERK, BAD, BDNF, p11, and 5-HT1B expression in the hippocampus of the depressed groups. In addition, there were an increase or a trend in p-CREB/CREB, p-ERK The antidepressant activities of Crocin/ Crocetin are possibly due to their effects on Serotonin and Corticosterone serum concentrations, NR2B expression, and the downstream signaling pathways. Furthermore, these natural carotenoids, like Fluoxetine, induced an increasing tendency in p11 and 5HT1B in depressed rats.
Sections du résumé
BACKGROUND
BACKGROUND
Depression is a debilitating condition that affects the mind and the individual's body. The improving effects of saffron on depression and anxiety have long been discussed, with limited information about the molecular mechanism of action.
HYPOTHESIS/PURPOSE
OBJECTIVE
Investigating the effect of saffron carotenoids, Crocin and Crocetin, on depression and anxiety in rats by emphasizing some signaling pathways involved.
STUDY DESIGN
METHODS
Depression and anxiety were induced in rats via unpredictable chronic mild stress (UCMS). Then different rat groups were treated with Crocin, Crocetin, Fluoxetine, and vehicle. Behavioral tests were done before and after treatment.
METHODS
METHODS
The serum Serotonin and Corticosterone and the expression of some hippocampal signaling proteins were studied. Furthermore, bioinformatics tools were used to predict the interactions of Crocin/ Crocetin with the Serotonin transporter and NMDA receptor subunit NR2B. Then, the patch-clamp was used to study the interaction of Crocetin with the NMDA receptor.
RESULTS
RESULTS
Various behavioral tests confirmed the induction of depression and the improvement of depression by these natural carotenoids. In addition, Crocin/ Crocetin significantly increased the decreased serum Serotonin and reduced the increased serum Corticosterone in the depressed groups. They also increased or caused a trend of increase in the CREB, ERK, BAD, BDNF, p11, and 5-HT1B expression in the hippocampus of the depressed groups. In addition, there were an increase or a trend in p-CREB/CREB, p-ERK
CONCLUSION
CONCLUSIONS
The antidepressant activities of Crocin/ Crocetin are possibly due to their effects on Serotonin and Corticosterone serum concentrations, NR2B expression, and the downstream signaling pathways. Furthermore, these natural carotenoids, like Fluoxetine, induced an increasing tendency in p11 and 5HT1B in depressed rats.
Identifiants
pubmed: 37506574
pii: S0944-7113(23)00350-1
doi: 10.1016/j.phymed.2023.154989
pii:
doi:
Substances chimiques
trans-sodium crocetinate
0
crocin
877GWI46C2
Brain-Derived Neurotrophic Factor
0
Serotonin Plasma Membrane Transport Proteins
0
Corticosterone
W980KJ009P
Fluoxetine
01K63SUP8D
Receptors, N-Methyl-D-Aspartate
0
Serotonin
333DO1RDJY
Carotenoids
36-88-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
154989Informations de copyright
Copyright © 2023. Published by Elsevier GmbH.
Déclaration de conflit d'intérêts
Declaration of Competing Interest I hereby declare that the disclosed information is correct and that no other situation of real, potential or apparent conflict of interest is known to me and other authors. I undertake to inform you of any change in these circumstances, including if an issue arises during the course of the submission or work itself.