Ginsenoside Rd attenuates ACTH-induced corticosterone secretion by blocking the MC2R-cAMP/PKA/CREB pathway in Y1 mouse adrenocortical cells.
Adrenal Cortex
/ cytology
Adrenocorticotropic Hormone
/ pharmacology
Animals
Blotting, Western
CREB-Binding Protein
/ metabolism
Cell Line, Tumor
Corticosterone
/ metabolism
Cyclic AMP
/ metabolism
Cyclic AMP-Dependent Protein Kinases
/ metabolism
Ginsenosides
/ pharmacology
Mice
Pregnenolone
/ metabolism
Receptor, Melanocortin, Type 2
/ metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
/ drug effects
Adrenocorticotropic hormone (ACTH)
Corticosterone secretion
Ginsenoside Rd
Melanocortin-2 receptor (MC2R)
cAMP/PKA/CREB signaling
Journal
Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521
Informations de publication
Date de publication:
15 Mar 2020
15 Mar 2020
Historique:
received:
28
10
2019
revised:
15
01
2020
accepted:
19
01
2020
pubmed:
24
1
2020
medline:
24
3
2020
entrez:
24
1
2020
Statut:
ppublish
Résumé
Higher levels of glucocorticoids (GCs), and impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis may cause or exacerbate the occurrence of metabolic and psychiatric disorders. It has been reported that ginseng saponin extract (GSE) has an inhibitory effect on the hyperactivity of the HPA axis induced by stresses and increased corticosterone level induced by intraperitoneal injection of adrenocorticotrophic hormone (ACTH) in mice. However, the molecular mechanisms by which GSE and its active ginsenosides inhibit corticosterone secretion remain elusive. Y1 mouse adrenocortical cells were treated with ACTH for up to 60 min to establish a cell model of corticosterone secretion. After treatment with different concentrations of GSE or ginsenoside monomers for 24 h prior to the addition of ACTH, analyses of cAMP content, PKA activity, and the levels of steroidogenesis regulators, melanocortin-2 receptor (MC2R), and melanocortin-2 receptor accessory protein (MRAP) in ACTH-induced Y1 cells were performed. We demonstrated that GSE inhibits ACTH-stimulated corticosterone production in Y1 cells by inhibiting factors critical for steroid synthesis. Ginsenoside Rd, an active ingredient of GSE, inhibits corticosterone secretion in the cells and impedes ACTH-induced corticosterone biosynthesis through down-regulation of proteins in the cAMP/PKA/CREB signaling pathway. In addition, Western blot and qPCR analyses showed that ginsenoside Rd attenuated the induction of MC2R and MRAP by ACTH. Our findings indicate that ginsenoside Rd inhibits ACTH-induced corticosterone production through blockading the MC2R-cAMP/PKA/CREB pathway in adrenocortical cells. Overall, this mechanism may represent an important therapeutic option for the treatment of stress-related disorders, further supporting the pharmacological benefits of ginseng.
Sections du résumé
BACKGROUND
BACKGROUND
Higher levels of glucocorticoids (GCs), and impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis may cause or exacerbate the occurrence of metabolic and psychiatric disorders. It has been reported that ginseng saponin extract (GSE) has an inhibitory effect on the hyperactivity of the HPA axis induced by stresses and increased corticosterone level induced by intraperitoneal injection of adrenocorticotrophic hormone (ACTH) in mice. However, the molecular mechanisms by which GSE and its active ginsenosides inhibit corticosterone secretion remain elusive.
MAIN METHODS
METHODS
Y1 mouse adrenocortical cells were treated with ACTH for up to 60 min to establish a cell model of corticosterone secretion. After treatment with different concentrations of GSE or ginsenoside monomers for 24 h prior to the addition of ACTH, analyses of cAMP content, PKA activity, and the levels of steroidogenesis regulators, melanocortin-2 receptor (MC2R), and melanocortin-2 receptor accessory protein (MRAP) in ACTH-induced Y1 cells were performed.
RESULTS
RESULTS
We demonstrated that GSE inhibits ACTH-stimulated corticosterone production in Y1 cells by inhibiting factors critical for steroid synthesis. Ginsenoside Rd, an active ingredient of GSE, inhibits corticosterone secretion in the cells and impedes ACTH-induced corticosterone biosynthesis through down-regulation of proteins in the cAMP/PKA/CREB signaling pathway. In addition, Western blot and qPCR analyses showed that ginsenoside Rd attenuated the induction of MC2R and MRAP by ACTH.
CONCLUSION
CONCLUSIONS
Our findings indicate that ginsenoside Rd inhibits ACTH-induced corticosterone production through blockading the MC2R-cAMP/PKA/CREB pathway in adrenocortical cells. Overall, this mechanism may represent an important therapeutic option for the treatment of stress-related disorders, further supporting the pharmacological benefits of ginseng.
Identifiants
pubmed: 31972205
pii: S0024-3205(20)30084-9
doi: 10.1016/j.lfs.2020.117337
pii:
doi:
Substances chimiques
Ginsenosides
0
Receptor, Melanocortin, Type 2
0
Pregnenolone
73R90F7MQ8
Adrenocorticotropic Hormone
9002-60-2
Cyclic AMP
E0399OZS9N
CREB-Binding Protein
EC 2.3.1.48
Crebbp protein, mouse
EC 2.3.1.48
Cyclic AMP-Dependent Protein Kinases
EC 2.7.11.11
Corticosterone
W980KJ009P
ginsenoside Rd
WB232T95AV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
117337Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest There were no financial or other conflicts of interest in designing, performing, or drafting this work.