Induction of EpRE-mediated gene expression by a series of mediterranean botanicals and their constituents

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Ethnopharmacological relevance: A variety of Mediterranean plant species, traditionally used for the prevention and treatment of several health conditions, contain ingredients with potential biological activity of which many remain unexplored. Among the beneficial health effects of bioactive phytochemicals is the activation of cellular defense mechanisms involving the activation of EpRE (electrophile responsive element) - mediated changes in gene expression. Aim of the study: The present study aimed to identify botanicals and their active constituents able to activate the EpRE mediated gene expression within a series of Mediterranean plant species known for their hepatoprotective and/or cardioprotective properties. Materials and methods: Methanolic extracts of 18 botanicals were prepared and tested for their ability to induce gene expression in EpRE-LUX reporter cells. Subsequently, LC-MS (Liquid Chromatography Mass Spectrometry) analysis combined with MAGMa (MS Annotation based on in silico Generated Metabolites) software for automated compound annotation was used to facilitate tentative identification of the active constituents within two of the active extracts. Selected annotated compounds were tested in the EpRE-LUX reporter gene assay followed by definite identification of the most active ones. Results: It appeared that 9 of the 18 extracts were able to activate EpRE-mediated gene expression. Many active ingredients of the methanolic extracts from Juglans regia and Rhamnus frangula were revealed. Among them, chrysophanol and aloe-emodin were confirmed to be active EpRE inducing ingredients and were definitely identified in the Rhamnus Frangula extract. Conclusions: The protective effect of half of the tested botanical varieties via the activation of EpRE-mediated gene expression was confirmed. The study also provided an example of how in vitro bioassays can be combined with LC-MS and the automated chemical annotation software MAGMa, to identify biologically active constituents in complex botanical extracts.

Original languageEnglish
Article number111940
Number of pages13
JournalJournal of Ethnopharmacology
Volume240
DOIs
Publication statusPublished - 10 Aug 2019

Fingerprint

Frangula
Rhamnus
Gene Expression
Liquid Chromatography
Mass Spectrometry
Software
Juglans
Health
Phytochemicals
Complex Mixtures
Reporter Genes
Biological Assay
Computer Simulation

Keywords

  • Aloe-emodin
  • Botanical extracts
  • Chrysophanol
  • EpRE/Nrf2
  • MAGMa
  • Rhamnus frangula

Cite this

@article{df6c038b66514fe5a20865b972b135b0,
title = "Induction of EpRE-mediated gene expression by a series of mediterranean botanicals and their constituents",
abstract = "Ethnopharmacological relevance: A variety of Mediterranean plant species, traditionally used for the prevention and treatment of several health conditions, contain ingredients with potential biological activity of which many remain unexplored. Among the beneficial health effects of bioactive phytochemicals is the activation of cellular defense mechanisms involving the activation of EpRE (electrophile responsive element) - mediated changes in gene expression. Aim of the study: The present study aimed to identify botanicals and their active constituents able to activate the EpRE mediated gene expression within a series of Mediterranean plant species known for their hepatoprotective and/or cardioprotective properties. Materials and methods: Methanolic extracts of 18 botanicals were prepared and tested for their ability to induce gene expression in EpRE-LUX reporter cells. Subsequently, LC-MS (Liquid Chromatography Mass Spectrometry) analysis combined with MAGMa (MS Annotation based on in silico Generated Metabolites) software for automated compound annotation was used to facilitate tentative identification of the active constituents within two of the active extracts. Selected annotated compounds were tested in the EpRE-LUX reporter gene assay followed by definite identification of the most active ones. Results: It appeared that 9 of the 18 extracts were able to activate EpRE-mediated gene expression. Many active ingredients of the methanolic extracts from Juglans regia and Rhamnus frangula were revealed. Among them, chrysophanol and aloe-emodin were confirmed to be active EpRE inducing ingredients and were definitely identified in the Rhamnus Frangula extract. Conclusions: The protective effect of half of the tested botanical varieties via the activation of EpRE-mediated gene expression was confirmed. The study also provided an example of how in vitro bioassays can be combined with LC-MS and the automated chemical annotation software MAGMa, to identify biologically active constituents in complex botanical extracts.",
keywords = "Aloe-emodin, Botanical extracts, Chrysophanol, EpRE/Nrf2, MAGMa, Rhamnus frangula",
author = "Georgia Papadi and Sebastiaan Wesseling and Troganis, {Anastassios N.} and Jacques Vervoort and Rietjens, {Ivonne M.C.M.}",
year = "2019",
month = "8",
day = "10",
doi = "10.1016/j.jep.2019.111940",
language = "English",
volume = "240",
journal = "Journal of Ethnopharmacology",
issn = "0378-8741",
publisher = "Elsevier",

}

Induction of EpRE-mediated gene expression by a series of mediterranean botanicals and their constituents. / Papadi, Georgia; Wesseling, Sebastiaan; Troganis, Anastassios N.; Vervoort, Jacques; Rietjens, Ivonne M.C.M.

In: Journal of Ethnopharmacology, Vol. 240, 111940, 10.08.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Induction of EpRE-mediated gene expression by a series of mediterranean botanicals and their constituents

AU - Papadi, Georgia

AU - Wesseling, Sebastiaan

AU - Troganis, Anastassios N.

AU - Vervoort, Jacques

AU - Rietjens, Ivonne M.C.M.

PY - 2019/8/10

Y1 - 2019/8/10

N2 - Ethnopharmacological relevance: A variety of Mediterranean plant species, traditionally used for the prevention and treatment of several health conditions, contain ingredients with potential biological activity of which many remain unexplored. Among the beneficial health effects of bioactive phytochemicals is the activation of cellular defense mechanisms involving the activation of EpRE (electrophile responsive element) - mediated changes in gene expression. Aim of the study: The present study aimed to identify botanicals and their active constituents able to activate the EpRE mediated gene expression within a series of Mediterranean plant species known for their hepatoprotective and/or cardioprotective properties. Materials and methods: Methanolic extracts of 18 botanicals were prepared and tested for their ability to induce gene expression in EpRE-LUX reporter cells. Subsequently, LC-MS (Liquid Chromatography Mass Spectrometry) analysis combined with MAGMa (MS Annotation based on in silico Generated Metabolites) software for automated compound annotation was used to facilitate tentative identification of the active constituents within two of the active extracts. Selected annotated compounds were tested in the EpRE-LUX reporter gene assay followed by definite identification of the most active ones. Results: It appeared that 9 of the 18 extracts were able to activate EpRE-mediated gene expression. Many active ingredients of the methanolic extracts from Juglans regia and Rhamnus frangula were revealed. Among them, chrysophanol and aloe-emodin were confirmed to be active EpRE inducing ingredients and were definitely identified in the Rhamnus Frangula extract. Conclusions: The protective effect of half of the tested botanical varieties via the activation of EpRE-mediated gene expression was confirmed. The study also provided an example of how in vitro bioassays can be combined with LC-MS and the automated chemical annotation software MAGMa, to identify biologically active constituents in complex botanical extracts.

AB - Ethnopharmacological relevance: A variety of Mediterranean plant species, traditionally used for the prevention and treatment of several health conditions, contain ingredients with potential biological activity of which many remain unexplored. Among the beneficial health effects of bioactive phytochemicals is the activation of cellular defense mechanisms involving the activation of EpRE (electrophile responsive element) - mediated changes in gene expression. Aim of the study: The present study aimed to identify botanicals and their active constituents able to activate the EpRE mediated gene expression within a series of Mediterranean plant species known for their hepatoprotective and/or cardioprotective properties. Materials and methods: Methanolic extracts of 18 botanicals were prepared and tested for their ability to induce gene expression in EpRE-LUX reporter cells. Subsequently, LC-MS (Liquid Chromatography Mass Spectrometry) analysis combined with MAGMa (MS Annotation based on in silico Generated Metabolites) software for automated compound annotation was used to facilitate tentative identification of the active constituents within two of the active extracts. Selected annotated compounds were tested in the EpRE-LUX reporter gene assay followed by definite identification of the most active ones. Results: It appeared that 9 of the 18 extracts were able to activate EpRE-mediated gene expression. Many active ingredients of the methanolic extracts from Juglans regia and Rhamnus frangula were revealed. Among them, chrysophanol and aloe-emodin were confirmed to be active EpRE inducing ingredients and were definitely identified in the Rhamnus Frangula extract. Conclusions: The protective effect of half of the tested botanical varieties via the activation of EpRE-mediated gene expression was confirmed. The study also provided an example of how in vitro bioassays can be combined with LC-MS and the automated chemical annotation software MAGMa, to identify biologically active constituents in complex botanical extracts.

KW - Aloe-emodin

KW - Botanical extracts

KW - Chrysophanol

KW - EpRE/Nrf2

KW - MAGMa

KW - Rhamnus frangula

U2 - 10.1016/j.jep.2019.111940

DO - 10.1016/j.jep.2019.111940

M3 - Article

VL - 240

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

SN - 0378-8741

M1 - 111940

ER -