The triterpenoid ursolic acid ameliorates stress in Caenorhabditis elegans by affecting the depression-associated genes skn-1 and prdx2

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000661732400012&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2021.153598
eISSN
1618-095X
Externe Identifier
  • Clarivate Analytics Document Solution ID: SS4OC
  • PubMed Identifier: 34111615
ISSN
0944-7113
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Adaptogen
  • Depression
  • Natural product
  • Reactive oxygen species
  • Stress
Artikelnummer
ARTN 153598
Datum der Veröffentlichung
2021
Status
Published
Titel
The triterpenoid ursolic acid ameliorates stress in <i>Caenorhabditis elegans</i> by affecting the depression-associated genes <i>skn-1</i> and <i>prdx2</i>
Sub types
  • Article
Ausgabe der Zeitschrift
88

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.1016/j.phymed.2021.153598
ISSN
0944-7113
Zeitschrift
Phytomedicine
Sprache
en
Artikelnummer
153598
Paginierung
153598 - 153598
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2021.153598
Datum der Datenerfassung
2023
Titel
The triterpenoid ursolic acid ameliorates stress in Caenorhabditis elegans by affecting the depression-associated genes skn-1 and prdx2
Ausgabe der Zeitschrift
88

Data source: Crossref

Abstract
<h4>Introduction</h4>Depression is one of the leading causes of death worldwide. Lower antioxidant concentrations and increased oxidative stress levels contribute to the development of depression. Effective and tolerable medications are urgently needed. Nrf2 and PRDX2 are promising targets in the treatment of oxidative stress and, therefore, promising for the development of novel antidepressants. Ursolic acid (UA), a natural triterpenoid found in various plants is known to exert neuroprotective and antioxidant effects. Skn-1 (which corresponds to human Nrf2) and prdx2 deficient mutants of the nematode Caenorhabditis elegans are suitable models to study the effect of UA on these targets. Additionally, stress assays are used to mimic stress or depressed state.<h4>Methods</h4>We examined the antioxidant activity of UA in Caenorhabditis elegans wildtype and skn-1- and prdx2-deficient strains by H<sub>2</sub>DCF-DA and juglone assays as well as osmotic and heat stress assays. Additionally, we analyzed the binding of UA to human PRDX2 and Skn-1 proteins by molecular docking and microscale thermophoresis.<h4>Results</h4>UA exerted strong antioxidant activities. Additionally, induction of stress resistance towards osmotic and heat stress was observed. qRT-PCR revealed that UA upregulated the gene expression of skn-1 and prdx2. Molecular docking studies supported these findings.<h4>Conclusion</h4>Our findings implicate that the strong antioxidant activity of UA may exert anti-depressive effects by its interaction with the Skn-1 transcription factor, which is part of a detoxification network, and the antioxidant PRDX2 protein, which protects the organism from the detrimental effects of radical oxygen species.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Autoren
DOI
10.1016/j.phymed.2021.153598
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 34111615
Open access
false
ISSN
0944-7113
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Animals
  • Caenorhabditis elegans
  • Reactive Oxygen Species
  • Triterpenes
  • DNA-Binding Proteins
  • Caenorhabditis elegans Proteins
  • Transcription Factors
  • Antidepressive Agents
  • Protective Agents
  • Antioxidants
  • Depression
  • Gene Expression Regulation
  • Oxidative Stress
  • Mutation
  • Peroxiredoxins
  • Stress, Physiological
  • Molecular Docking Simulation
  • Ursolic Acid
Sprache
eng
Medium
Print-Electronic
Online publication date
2021
Paginierung
153598
Datum der Veröffentlichung
2021
Status
Published
Datum der Datenerfassung
2021
Titel
The triterpenoid ursolic acid ameliorates stress in Caenorhabditis elegans by affecting the depression-associated genes skn-1 and prdx2.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
88

Data source: Europe PubMed Central

Abstract
INTRODUCTION: Depression is one of the leading causes of death worldwide. Lower antioxidant concentrations and increased oxidative stress levels contribute to the development of depression. Effective and tolerable medications are urgently needed. Nrf2 and PRDX2 are promising targets in the treatment of oxidative stress and, therefore, promising for the development of novel antidepressants. Ursolic acid (UA), a natural triterpenoid found in various plants is known to exert neuroprotective and antioxidant effects. Skn-1 (which corresponds to human Nrf2) and prdx2 deficient mutants of the nematode Caenorhabditis elegans are suitable models to study the effect of UA on these targets. Additionally, stress assays are used to mimic stress or depressed state. METHODS: We examined the antioxidant activity of UA in Caenorhabditis elegans wildtype and skn-1- and prdx2-deficient strains by H2DCF-DA and juglone assays as well as osmotic and heat stress assays. Additionally, we analyzed the binding of UA to human PRDX2 and Skn-1 proteins by molecular docking and microscale thermophoresis. RESULTS: UA exerted strong antioxidant activities. Additionally, induction of stress resistance towards osmotic and heat stress was observed. qRT-PCR revealed that UA upregulated the gene expression of skn-1 and prdx2. Molecular docking studies supported these findings. CONCLUSION: Our findings implicate that the strong antioxidant activity of UA may exert anti-depressive effects by its interaction with the Skn-1 transcription factor, which is part of a detoxification network, and the antioxidant PRDX2 protein, which protects the organism from the detrimental effects of radical oxygen species.
Date of acceptance
2021
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/34111615
DOI
10.1016/j.phymed.2021.153598
eISSN
1618-095X
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Adaptogen
  • Depression
  • Natural product
  • Reactive oxygen species
  • Stress
  • Animals
  • Antidepressive Agents
  • Antioxidants
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Depression
  • Gene Expression Regulation
  • Molecular Docking Simulation
  • Mutation
  • Oxidative Stress
  • Peroxiredoxins
  • Protective Agents
  • Reactive Oxygen Species
  • Stress, Physiological
  • Transcription Factors
  • Triterpenes
  • Ursolic Acid
Sprache
eng
Country
Germany
Paginierung
153598
PII
S0944-7113(21)00140-9
Datum der Veröffentlichung
2021
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
The triterpenoid ursolic acid ameliorates stress in Caenorhabditis elegans by affecting the depression-associated genes skn-1 and prdx2.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
88

Data source: PubMed

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