Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells

Autoren

Alexander Panossian
Rebecca Hamm
Onat Kadioglu
Georg Wikman
Thomas Efferth

DOI

10.3389/fnins.2013.00016

eISSN

1662-4548

Zeitschrift

Frontiers in Neuroscience

Online publication date

2013

Status

Published online

Herausgeber

Frontiers Media SA

Herausgeber URL

http://dx.doi.org/10.3389/fnins.2013.00016

Datum der Datenerfassung

2015

Titel

Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells

Ausgabe der Zeitschrift

7

Data source: Crossref

Abstract

Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents - extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipase C (PLC), and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by down-regulation of adenylate cyclase gene ADC2Y and up-regulation of phosphodiesterase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. Down-regulation of cAMP by adaptogens may decrease cAMP-dependent protein kinase A activity in various cells resulting in inhibition stress-induced catabolic transformations and saving of ATP for many ATP-dependant metabolic transformations. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific PLC and phosphatidylinositol 3-kinases (PI3Ks), key players for the regulation of NF-κB-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor (2.9-22.6 fold down-regulation), cholesterol ester transfer protein (5.1-10.6 fold down-regulation), heat shock protein Hsp70 (3.0-45.0 fold up-regulation), serpin peptidase inhibitor (neuroserpin), and 5-HT3 receptor of serotonin (2.2-6.6 fold down-regulation). These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental, and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. These interactions can have an influence on transcriptional control of metabolic regulation both on the cellular level and the level of the whole organism. Merging of deregulated genes array profiles and intracellular networks is specific to the new substance with unique pharmacological characteristics. Presumably, this phenomenon could be used to eliminate undesirable effects (e.g., toxic effects) and increase the selectivity of pharmacological intervention.

Addresses

Swedish Herbal Institute Research and Development Göteborg, Sweden.

Autoren

Alexander Panossian
Rebecca Hamm
Onat Kadioglu
Georg Wikman
Thomas Efferth
Thomas Efferth

DOI

10.3389/fnins.2013.00016

eISSN

1662-453X

Externe Identifier

PubMed Identifier: 23430930
PubMed Central ID: PMC3576868

Open access

true

ISSN

1662-4548

Zeitschrift

Frontiers in neuroscience

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2013

Open access status

Open Access

Paginierung

16

Datum der Veröffentlichung

2013

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2013

Titel

Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

7

Files

https://www.frontiersin.org/articles/10.3389/fnins.2013.00016/pdf https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23430930/pdf/?tool=EBI https://europepmc.org/articles/PMC3576868?pdf=render

Data source: Europe PubMed Central

Abstract

Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents - extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipase C (PLC), and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by down-regulation of adenylate cyclase gene ADC2Y and up-regulation of phosphodiesterase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. Down-regulation of cAMP by adaptogens may decrease cAMP-dependent protein kinase A activity in various cells resulting in inhibition stress-induced catabolic transformations and saving of ATP for many ATP-dependant metabolic transformations. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific PLC and phosphatidylinositol 3-kinases (PI3Ks), key players for the regulation of NF-κB-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor (2.9-22.6 fold down-regulation), cholesterol ester transfer protein (5.1-10.6 fold down-regulation), heat shock protein Hsp70 (3.0-45.0 fold up-regulation), serpin peptidase inhibitor (neuroserpin), and 5-HT3 receptor of serotonin (2.2-6.6 fold down-regulation). These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental, and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. These interactions can have an influence on transcriptional control of metabolic regulation both on the cellular level and the level of the whole organism. Merging of deregulated genes array profiles and intracellular networks is specific to the new substance with unique pharmacological characteristics. Presumably, this phenomenon could be used to eliminate undesirable effects (e.g., toxic effects) and increase the selectivity of pharmacological intervention.

Date of acceptance

2013

Autoren

Alexander Panossian
Rebecca Hamm
Onat Kadioglu
Georg Wikman
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/23430930

DOI

10.3389/fnins.2013.00016

Externe Identifier

PubMed Central ID: PMC3576868

ISSN

1662-4548

Zeitschrift

Front Neurosci

Schlüsselwörter

ADAPT-232
Eleutherococcus senticosus
Rhodiola rosea
Schisandra chinensis
eleutheroside E
pharmacogenomics
salidroside
schizandrin B

Sprache

eng

Country

Switzerland

Paginierung

16

Datum der Veröffentlichung

2013

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2013

Titel

Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells.

Sub types

Journal Article

Ausgabe der Zeitschrift

7

Data source: PubMed

Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells

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