Ursolic acid ameliorates stress and reactive oxygen species in C. elegans knockout mutants by the dopamine Dop1 and Dop3 receptors

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000605579700031&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2020.153439
eISSN
1618-095X
Externe Identifier
  • Clarivate Analytics Document Solution ID: PP0SH
  • PubMed Identifier: 33352493
ISSN
0944-7113
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • C. elegans
  • depression
  • dopamine
  • molecular docking
  • phytochemical
  • stress
Artikelnummer
ARTN 153439
Datum der Veröffentlichung
2021
Status
Published
Titel
Ursolic acid ameliorates stress and reactive oxygen species in <i>C</i>. <i>elegans</i> knockout mutants by the dopamine Dop1 and Dop3 receptors
Sub types
  • Article
Ausgabe der Zeitschrift
81

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.1016/j.phymed.2020.153439
ISSN
0944-7113
Zeitschrift
Phytomedicine
Sprache
en
Artikelnummer
153439
Paginierung
153439 - 153439
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2020.153439
Datum der Datenerfassung
2022
Titel
Ursolic acid ameliorates stress and reactive oxygen species in C. elegans knockout mutants by the dopamine Dop1 and Dop3 receptors
Ausgabe der Zeitschrift
81

Data source: Crossref

Abstract
<h4>Background</h4>Depression and stress-related disorders are leading causes of death worldwide. Standard treatments elevating serotonin or noradrenaline levels are not sufficiently effective and cause adverse side effects. A connection between dopamine pathways and stress-related disorders has been suggested. Compounds derived from herbal medicine could be a promising alternative. We examined the neuroprotective effects of ursolic acid (UA) by focusing on dopamine signalling.<h4>Methods</h4>Trolox equivalent capacity assay was used to determine the antioxidant activities of UA in vitro. C. elegans N2 wildtype and dopamine receptor-knockout mutants (dop1-deficient RB665 and dop3-deficient LX703 strains) were used as in vivo models. H<sub>2</sub>DCFDA and acute juglone assays were applied to determine the antioxidant activity in dependency of dopamine pathways in vivo. Stress was assessed by heat and acute osmotic stress assays. The influence of UA on overall survival was analyzed by a life span assay. The dop1 and dop3 mRNA expression was determined by real time RT-PCR. We also examined the binding affinity of UA towards C. elegans Dop1 and Dop3 receptors as well as human dopamine receptors D1 and D3 by molecular docking.<h4>Results</h4>Antioxidant activity assays showed that UA exerts strong antioxidant activity. UA increased resistance towards oxidative, osmotic and heat stress. Additionally, UA increased life span of nematodes. Moreover, dop1 and dop3 gene expression was significantly enhanced upon UA treatment. Docking analysis revealed stronger binding affinity of UA to C. elegans and human dopamine receptors than the natural ligand, dopamine. Binding to Dop1 was stronger than to Dop3.<h4>Conclusion</h4>UA reduced stress-dependent ROS generation and acted through Dop1 and to a lesser extent through Dop3 to reduce stress and prolong life span in C. elegans. These results indicate that UA could be a promising lead compound for the development of new antidepressant medications.
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.2020.153439
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 33352493
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft:
Open access
false
ISSN
0944-7113
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Animals
  • Humans
  • Caenorhabditis elegans
  • Reactive Oxygen Species
  • Dopamine
  • Triterpenes
  • Caenorhabditis elegans Proteins
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Antioxidants
  • Signal Transduction
  • Longevity
  • Mutation
  • Receptors, Dopamine D3
  • Stress, Physiological
  • Gene Knockout Techniques
  • Molecular Docking Simulation
  • Ursolic Acid
Sprache
eng
Medium
Print-Electronic
Online publication date
2020
Paginierung
153439
Datum der Veröffentlichung
2021
Status
Published
Datum der Datenerfassung
2020
Titel
Ursolic acid ameliorates stress and reactive oxygen species in C. elegans knockout mutants by the dopamine Dop1 and Dop3 receptors.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
81

Data source: Europe PubMed Central

Abstract
BACKGROUND: Depression and stress-related disorders are leading causes of death worldwide. Standard treatments elevating serotonin or noradrenaline levels are not sufficiently effective and cause adverse side effects. A connection between dopamine pathways and stress-related disorders has been suggested. Compounds derived from herbal medicine could be a promising alternative. We examined the neuroprotective effects of ursolic acid (UA) by focusing on dopamine signalling. METHODS: Trolox equivalent capacity assay was used to determine the antioxidant activities of UA in vitro. C. elegans N2 wildtype and dopamine receptor-knockout mutants (dop1-deficient RB665 and dop3-deficient LX703 strains) were used as in vivo models. H2DCFDA and acute juglone assays were applied to determine the antioxidant activity in dependency of dopamine pathways in vivo. Stress was assessed by heat and acute osmotic stress assays. The influence of UA on overall survival was analyzed by a life span assay. The dop1 and dop3 mRNA expression was determined by real time RT-PCR. We also examined the binding affinity of UA towards C. elegans Dop1 and Dop3 receptors as well as human dopamine receptors D1 and D3 by molecular docking. RESULTS: Antioxidant activity assays showed that UA exerts strong antioxidant activity. UA increased resistance towards oxidative, osmotic and heat stress. Additionally, UA increased life span of nematodes. Moreover, dop1 and dop3 gene expression was significantly enhanced upon UA treatment. Docking analysis revealed stronger binding affinity of UA to C. elegans and human dopamine receptors than the natural ligand, dopamine. Binding to Dop1 was stronger than to Dop3. CONCLUSION: UA reduced stress-dependent ROS generation and acted through Dop1 and to a lesser extent through Dop3 to reduce stress and prolong life span in C. elegans. These results indicate that UA could be a promising lead compound for the development of new antidepressant medications.
Date of acceptance
2020
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/33352493
DOI
10.1016/j.phymed.2020.153439
eISSN
1618-095X
Zeitschrift
Phytomedicine
Schlüsselwörter
  • C elegans
  • depression
  • dopamine
  • molecular docking
  • phytochemical
  • stress
  • Animals
  • Antioxidants
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Dopamine
  • Gene Knockout Techniques
  • Humans
  • Longevity
  • Molecular Docking Simulation
  • Mutation
  • Reactive Oxygen Species
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Signal Transduction
  • Stress, Physiological
  • Triterpenes
  • Ursolic Acid
Sprache
eng
Country
Germany
Paginierung
153439
PII
S0944-7113(20)30270-1
Datum der Veröffentlichung
2021
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
Ursolic acid ameliorates stress and reactive oxygen species in C. elegans knockout mutants by the dopamine Dop1 and Dop3 receptors.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
81

Data source: PubMed

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