Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: An interactive pathway analysis of the downstream effects using RNA microarray data

Publication type:
Journal article
Metadata:
Autoren
  • Alexander Panossian
  • Rebecca Hamm
  • Georg Wikman
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000341741900015&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2014.07.008
eISSN
1618-095X
Externe Identifier
  • Clarivate Analytics Document Solution ID: AP0HK
  • PubMed Identifier: 25172797
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Pharmacogenomics
  • Rhodiola rosea
  • Salidroside
  • Triandrin
  • Tyrosol
Paginierung
1325 - 1348
Datum der Veröffentlichung
2014
Status
Published
Titel
Mechanism of action of <i>Rhodiola</i>, salidroside, tyrosol and triandrin in isolated neuroglial cells: An interactive pathway analysis of the downstream effects using RNA microarray data
Sub types
  • Article
Ausgabe der Zeitschrift
21

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Alexander Panossian
  • Rebecca Hamm
  • Georg Wikman
  • Thomas Efferth
DOI
10.1016/j.phymed.2014.07.008
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine
Sprache
en
Paginierung
1325 - 1348
Datum der Veröffentlichung
2014
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2014.07.008
Datum der Datenerfassung
2024
Titel
Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: An interactive pathway analysis of the downstream effects using RNA microarray data
Ausgabe der Zeitschrift
21

Data source: Crossref

Abstract
<h4>Aim</h4>The aim of this study was to identify the targets (genes, interactive signaling pathways, and molecular networks) of Rhodiola rosea extract in isolated neuroglia cells and to predict the effects of Rhodiola extract on cellular functions and diseases. In addition, the potential mechanism of action of Rhodiola rosea extract was elucidated, and the "active principle" among the three isolated constituents (salidroside, triandrin, and tyrosol) was identified.<h4>Methods</h4>Gene expression profiling was performed using the T98G human neuroglia cell line after treatment with the Rhodiola rosea SHR-5 extract and several of its individual constituents (salidroside, triandrin and tyrosol). An interactive pathway analysis of the downstream effects was performed using datasets containing significantly up- and down-regulated genes, and the effects on cellular functions and diseases were predicted.<h4>Results</h4>In total, the expression of 1062 genes was deregulated by the Rhodiola extract (631 analyzed, 336 - up-regulated, 295 - down-regulated), and 1052, 1062, and 1057 genes were deregulated by salidroside, triandrin, and tyrosol, respectively. The analysis of the downstream effects shows that the most significant effects of Rhodiola are associated with cardiovascular (72 deregulated genes), metabolic (63 genes), gastrointestinal (163 genes), neurological (95 genes), endocrine (60 genes), behavioral (50 genes), and psychological disorders (62 genes). The most significantly affected canonical pathways across the entire dataset, which contains the 1062 genes deregulated by Rhodiola, were the following: (a) communication between innate and adaptive immune cells, (b) eNOS signaling, (c) altered T and B cell signaling in rheumatoid arthritis, (d) axonal guidance signaling, (e) G-protein coupled receptor signaling, (f) glutamate receptor signaling, (g) ephrin receptor signaling, (h) cAMP-mediated, and (i) atherosclerosis signaling pathways. Genes associated with behavior and behavioral diseases were identified within intracellular signaling pathways (d) through (h). The analysis of the downstream effects predicted decreases in emotional and aggressive behavior, which corroborates the results from preclinical and clinical studies of the use of Rhodiola for the treatment of depression and anxiety. Of the 17 genes that regulate emotional behavior, nine exhibit expression patterns that are consistent with decreases in emotional behavior (z-score -2.529), and all five relevant genes are expressed in a manner consistent with decreases in aggressive behavior (z-score -2.197). A decrease in seizures and infarct sizes and an increase in the chemotaxis of cells were predicted to accompany the decrease in emotional and aggressive behaviors.<h4>Conclusions</h4>Rhodiola exhibits a multi-targeted effect on transcription to regulate the cellular response, affecting the various signaling pathways and molecular networks associated with beneficial effects on emotional behavior, particularly aggressive behavior, and with psychological, neurological, cardiovascular, metabolic, endocrine, and gastrointestinal disorders. Each of the purified compounds has its own pharmacological profile, which is both similar to and different from that of the total Rhodiola extract. In general, several compounds contribute to the specific cellular or/and physiological function of the extract in various diseases.
Addresses
  • Swedish Herbal Institute Research and Development, Göteborg, Sweden. Electronic address: alexander.panossian@shi.se.
Autoren
  • Alexander Panossian
  • Rebecca Hamm
  • Georg Wikman
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1016/j.phymed.2014.07.008
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 25172797
Open access
false
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Neuroglia
  • Cell Line
  • Humans
  • Rhodiola
  • Phenylethyl Alcohol
  • Phenols
  • Glucosides
  • Plant Extracts
  • Oligonucleotide Array Sequence Analysis
  • Gene Expression Profiling
  • Signal Transduction
  • Gene Expression Regulation
  • Transcriptome
Sprache
eng
Medium
Print-Electronic
Online publication date
2014
Paginierung
1325 - 1348
Datum der Veröffentlichung
2014
Status
Published
Datum der Datenerfassung
2014
Titel
Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: an interactive pathway analysis of the downstream effects using RNA microarray data.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
21

Data source: Europe PubMed Central

Abstract
AIM: The aim of this study was to identify the targets (genes, interactive signaling pathways, and molecular networks) of Rhodiola rosea extract in isolated neuroglia cells and to predict the effects of Rhodiola extract on cellular functions and diseases. In addition, the potential mechanism of action of Rhodiola rosea extract was elucidated, and the "active principle" among the three isolated constituents (salidroside, triandrin, and tyrosol) was identified. METHODS: Gene expression profiling was performed using the T98G human neuroglia cell line after treatment with the Rhodiola rosea SHR-5 extract and several of its individual constituents (salidroside, triandrin and tyrosol). An interactive pathway analysis of the downstream effects was performed using datasets containing significantly up- and down-regulated genes, and the effects on cellular functions and diseases were predicted. RESULTS: In total, the expression of 1062 genes was deregulated by the Rhodiola extract (631 analyzed, 336 - up-regulated, 295 - down-regulated), and 1052, 1062, and 1057 genes were deregulated by salidroside, triandrin, and tyrosol, respectively. The analysis of the downstream effects shows that the most significant effects of Rhodiola are associated with cardiovascular (72 deregulated genes), metabolic (63 genes), gastrointestinal (163 genes), neurological (95 genes), endocrine (60 genes), behavioral (50 genes), and psychological disorders (62 genes). The most significantly affected canonical pathways across the entire dataset, which contains the 1062 genes deregulated by Rhodiola, were the following: (a) communication between innate and adaptive immune cells, (b) eNOS signaling, (c) altered T and B cell signaling in rheumatoid arthritis, (d) axonal guidance signaling, (e) G-protein coupled receptor signaling, (f) glutamate receptor signaling, (g) ephrin receptor signaling, (h) cAMP-mediated, and (i) atherosclerosis signaling pathways. Genes associated with behavior and behavioral diseases were identified within intracellular signaling pathways (d) through (h). The analysis of the downstream effects predicted decreases in emotional and aggressive behavior, which corroborates the results from preclinical and clinical studies of the use of Rhodiola for the treatment of depression and anxiety. Of the 17 genes that regulate emotional behavior, nine exhibit expression patterns that are consistent with decreases in emotional behavior (z-score -2.529), and all five relevant genes are expressed in a manner consistent with decreases in aggressive behavior (z-score -2.197). A decrease in seizures and infarct sizes and an increase in the chemotaxis of cells were predicted to accompany the decrease in emotional and aggressive behaviors. CONCLUSIONS: Rhodiola exhibits a multi-targeted effect on transcription to regulate the cellular response, affecting the various signaling pathways and molecular networks associated with beneficial effects on emotional behavior, particularly aggressive behavior, and with psychological, neurological, cardiovascular, metabolic, endocrine, and gastrointestinal disorders. Each of the purified compounds has its own pharmacological profile, which is both similar to and different from that of the total Rhodiola extract. In general, several compounds contribute to the specific cellular or/and physiological function of the extract in various diseases.
Date of acceptance
2014
Autoren
  • Alexander Panossian
  • Rebecca Hamm
  • Georg Wikman
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/25172797
DOI
10.1016/j.phymed.2014.07.008
eISSN
1618-095X
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Pharmacogenomics
  • Rhodiola rosea
  • Salidroside
  • Triandrin
  • Tyrosol
  • Cell Line
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Glucosides
  • Humans
  • Neuroglia
  • Oligonucleotide Array Sequence Analysis
  • Phenols
  • Phenylethyl Alcohol
  • Plant Extracts
  • Rhodiola
  • Signal Transduction
  • Transcriptome
Sprache
eng
Country
Germany
Paginierung
1325 - 1348
PII
S0944-7113(14)00291-8
Datum der Veröffentlichung
2014
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: an interactive pathway analysis of the downstream effects using RNA microarray data.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
21

Data source: PubMed

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