Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin 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:000648076100001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1055/a-1349-3870
eISSN
1439-0795
Externe Identifier
  • Clarivate Analytics Document Solution ID: UP9EV
  • PubMed Identifier: 33957677
ISSN
0176-3679
Ausgabe der Veröffentlichung
05
Zeitschrift
PHARMACOPSYCHIATRY
Schlüsselwörter
  • Caenorhabditis elegans
  • depression
  • lifespan
  • molecular docking
  • stress
Paginierung
215 - 223
Datum der Veröffentlichung
2021
Status
Published
Titel
Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors
Sub types
  • Article
Ausgabe der Zeitschrift
54

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>ABSTRACT</jats:title><jats:p> Introduction Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods.</jats:p><jats:p> Methods WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6.</jats:p><jats:p> Results WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5.</jats:p><jats:p> Limitations Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings.</jats:p><jats:p> Conclusion WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.</jats:p>
Autoren
DOI
10.1055/a-1349-3870
eISSN
1439-0795
ISSN
0176-3679
Ausgabe der Veröffentlichung
05
Zeitschrift
Pharmacopsychiatry
Sprache
en
Online publication date
2021
Paginierung
215 - 223
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Georg Thieme Verlag KG
Herausgeber URL
http://dx.doi.org/10.1055/a-1349-3870
Datum der Datenerfassung
2021
Titel
Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors
Ausgabe der Zeitschrift
54

Data source: Crossref

Abstract
<h4>Introduction</h4>Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods.<h4>Methods</h4>WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H<sub>2</sub>DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (<i>ser-1, ser-4, ser-7</i>) and serotonin transporter (<i>mod-5</i>). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6.<h4>Results</h4>WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5.<h4>Limitations</h4>Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings.<h4>Conclusion</h4>WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
Autoren
DOI
10.1055/a-1349-3870
eISSN
1439-0795
Externe Identifier
  • PubMed Identifier: 33957677
Open access
false
ISSN
0176-3679
Ausgabe der Veröffentlichung
5
Zeitschrift
Pharmacopsychiatry
Schlüsselwörter
  • Animals
  • Animals, Genetically Modified
  • Humans
  • Caenorhabditis elegans
  • Fluoxetine
  • Receptors, Serotonin
  • Antidepressive Agents
  • Depression
  • Synaptic Transmission
  • Oxidative Stress
  • Longevity
  • Serotonin Plasma Membrane Transport Proteins
  • Withanolides
  • COVID-19
  • SARS-CoV-2
Sprache
eng
Medium
Print-Electronic
Online publication date
2021
Paginierung
215 - 223
Datum der Veröffentlichung
2021
Status
Published
Datum der Datenerfassung
2021
Titel
Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
54

Data source: Europe PubMed Central

Abstract
INTRODUCTION: Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods. METHODS: WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6. RESULTS: WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5. LIMITATIONS: Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings. CONCLUSION: WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/33957677
DOI
10.1055/a-1349-3870
eISSN
1439-0795
Ausgabe der Veröffentlichung
5
Zeitschrift
Pharmacopsychiatry
Schlüsselwörter
  • Animals
  • Animals, Genetically Modified
  • Antidepressive Agents
  • COVID-19
  • Caenorhabditis elegans
  • Depression
  • Fluoxetine
  • Humans
  • Longevity
  • Oxidative Stress
  • Receptors, Serotonin
  • SARS-CoV-2
  • Serotonin Plasma Membrane Transport Proteins
  • Synaptic Transmission
  • Withanolides
Sprache
eng
Country
Germany
Paginierung
215 - 223
Datum der Veröffentlichung
2021
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
54

Data source: PubMed

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