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Updated: Nov 6, 2025
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors
1Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
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.
Insights
Withanone (WN) from Withania somnifera activates the serotonin system, reducing stress symptoms and extending lifespan in C. elegans. This natural compound shows potential for developing novel depression treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Depression causes significant global mortality, necessitating new, affordable treatments with fewer side effects.
- The COVID-19 pandemic is projected to exacerbate depression rates worldwide.
- Withania somnifera's withanone (WN) is explored for its potential antidepressant effects.
Purpose of the Study:
- To investigate the effect of withanone (WN) on the serotonin system in Caenorhabditis elegans.
- To evaluate WN's impact on stress responses and lifespan.
- To analyze WN's binding affinity to serotonin receptors and transporters.
Main Methods:
- Administered WN and fluoxetine to wild-type and knockout C. elegans strains.
- Assessed oxidative, osmotic, and heat stress responses, and lifespan.
- Utilized quantitative real-time RT-PCR for gene expression analysis of serotonin system components.
- Performed in silico molecular docking to determine WN's binding affinities.
Main Results:
- Withanone (WN) demonstrated ROS scavenging activity and prolonged lifespan in C. elegans.
- WN significantly upregulated the expression of serotonin receptor (Ser-1, Ser-4, Ser-7) and transporter (Mod-5) genes.
- In silico analysis confirmed high binding affinities of WN to key serotonin system targets.
Conclusions:
- Withanone (WN) ameliorates depression-associated stress symptoms by modulating the serotonin system.
- WN shows promise as a potential therapeutic candidate for depression drug development.
- Further research is required to validate these findings in mammalian models.
