Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons.
Alkaloids
/ pharmacology
Animals
Astrocytes
/ physiology
Brain-Derived Neurotrophic Factor
/ metabolism
Cell Count
Cell Survival
/ drug effects
Cerebral Cortex
Corticosterone
/ adverse effects
Dose-Response Relationship, Drug
Flavonoids
/ antagonists & inhibitors
Gene Expression
/ drug effects
Male
Neurons
/ metabolism
Neuroprotective Agents
/ pharmacology
Polyphenols
/ pharmacology
Primary Cell Culture
Propiophenones
/ antagonists & inhibitors
Quercetin
/ pharmacology
Rats
Tacrolimus Binding Proteins
/ biosynthesis
cortical neurons
corticosterone
polyphenols
stress
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
02
07
2019
revised:
18
09
2019
accepted:
04
12
2019
pubmed:
10
12
2019
medline:
26
5
2020
entrez:
9
12
2019
Statut:
ppublish
Résumé
Polyphenols are phytochemicals that have been associated with therapeutic effects in stress-related disorders. Indeed, studies suggest that polyphenols exert significant neuroprotection against multiple neuronal injuries, including oxidative stress and neuroinflammation, but the mechanisms are unclear. Evidence indicates that polyphenol neuroprotection may be mediated by activation of Nrf2, a transcription factor associated with antioxidant and cell survival responses. On the other hand, in stress-linked disorders, Fkbp5 is a novel molecular target for treatment because of its capacity to regulate glucocorticoid receptor sensitivity. However, it is not clear the role Fkbp5 plays in polyphenol-mediated stress modulation. In this study, the neuroprotective effects and mechanisms of the naturally derived polyphenols xanthohumol and quercetin against cytotoxicity induced by corticosterone were investigated in primary cortical cells. Primary cortical cells containing both neurons and astrocytes were pre-incubated with different concentrations of quercetin and xanthohumol to examine the neuroprotective effects of polyphenols on cell viability, morphology, and gene expression following corticosterone insult. Both polyphenols tested prevented the reduction of cell viability and alterations of neuronal/astrocytic numbers due to corticosterone exposure. Basal levels of Bdnf mRNA were also decreased after corticosterone insult; however, this was reversed by both polyphenol treatments. Interestingly, the Nrf2 inhibitor blocked xanthohumol but not quercetin-mediated neuroprotection. In contrast, we found that Fkbp5 expression is exclusively modulated by quercetin. These results suggest that naturally derived polyphenols protect cortical cells against corticosterone-induced cytotoxicity and enhance cell survival via modulation of the Nrf2 pathway and expression of Fkbp5.
Sections du résumé
BACKGROUND
Polyphenols are phytochemicals that have been associated with therapeutic effects in stress-related disorders. Indeed, studies suggest that polyphenols exert significant neuroprotection against multiple neuronal injuries, including oxidative stress and neuroinflammation, but the mechanisms are unclear. Evidence indicates that polyphenol neuroprotection may be mediated by activation of Nrf2, a transcription factor associated with antioxidant and cell survival responses. On the other hand, in stress-linked disorders, Fkbp5 is a novel molecular target for treatment because of its capacity to regulate glucocorticoid receptor sensitivity. However, it is not clear the role Fkbp5 plays in polyphenol-mediated stress modulation. In this study, the neuroprotective effects and mechanisms of the naturally derived polyphenols xanthohumol and quercetin against cytotoxicity induced by corticosterone were investigated in primary cortical cells.
METHODS
Primary cortical cells containing both neurons and astrocytes were pre-incubated with different concentrations of quercetin and xanthohumol to examine the neuroprotective effects of polyphenols on cell viability, morphology, and gene expression following corticosterone insult.
RESULTS
Both polyphenols tested prevented the reduction of cell viability and alterations of neuronal/astrocytic numbers due to corticosterone exposure. Basal levels of Bdnf mRNA were also decreased after corticosterone insult; however, this was reversed by both polyphenol treatments. Interestingly, the Nrf2 inhibitor blocked xanthohumol but not quercetin-mediated neuroprotection. In contrast, we found that Fkbp5 expression is exclusively modulated by quercetin.
CONCLUSIONS
These results suggest that naturally derived polyphenols protect cortical cells against corticosterone-induced cytotoxicity and enhance cell survival via modulation of the Nrf2 pathway and expression of Fkbp5.
Identifiants
pubmed: 31812985
pii: 5669943
doi: 10.1093/ijnp/pyz052
pmc: PMC6929673
doi:
Substances chimiques
Alkaloids
0
Bdnf protein, rat
0
Brain-Derived Neurotrophic Factor
0
Flavonoids
0
Neuroprotective Agents
0
Polyphenols
0
Propiophenones
0
trigonelline
3NQ9N60I00
Quercetin
9IKM0I5T1E
Tacrolimus Binding Proteins
EC 5.2.1.-
tacrolimus binding protein 5
EC 5.2.1.8
xanthohumol
T4467YT1NT
Corticosterone
W980KJ009P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
765-777Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.
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