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Molecules ; 26(7)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1167670


Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.

Antidepressive Agents/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Aging/drug effects , Aging/physiology , Animals , Antioxidants/pharmacology , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Gene Knockout Techniques , Heat-Shock Response/drug effects , Longevity/drug effects , Longevity/genetics , Longevity/physiology , Mutation , Osmotic Pressure/drug effects , Oxidative Stress/drug effects , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism
Phytomedicine ; 84: 153482, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1051912


INTRODUCTION: Approximately 300 million people worldwide suffer from depression. The COVID-19 crisis may dramatically increase these numbers. Severe side effects and resistance development limit the use of standard antidepressants. The steroidal lactone withanolide A (WA) from Withania somnifera may be a promising alternative. Caenorhabditis elegans was used as model to explore WA's anti-depressive and anti-stress potential. METHODS: C. elegans wildtype (N2) and deficient strains (AQ866, DA1814, DA2100, DA2109 and MT9772) were used to assess oxidative, osmotic or heat stress as measured by generation of reactive oxygen species (ROS), determination of lifespan, and mRNA expression of serotonin receptor (ser-1, ser-4, ser-7) and serotonin transporter genes (mod-5). The protective effect of WA was compared to fluoxetine as clinically established antidepressant. Additionally, WA's effect on lifespan was determined. Furthermore, the binding affinities and pKi values of WA, fluoxetine and serotonin as natural ligand to Ser-1, Ser-4, Ser-7, Mod-5 and their human orthologues proteins were calculated by molecular docking. RESULTS: Baseline oxidative stress was higher in deficient than wildtype worms. WA and fluoxetine reduced ROS levels in all strains except MT9772. WA and fluoxetine prolonged survival times in wildtype and mutants under osmotic stress. WA but not fluoxetine increased lifespan of all heat-stressed C. elegans strains except DA2100. Furthermore, WA but not fluoxetine extended lifespan in all non-stressed C. elegans strains. WA also induced mRNA expression of serotonin receptors and transporters in wildtype and mutants. WA bound with higher affinity and lower pKi values to all C. elegans and human serotonin receptors and transporters than serotonin, indicating that WA may competitively displaced serotonin from the binding pockets of these proteins. CONCLUSION: WA reduced stress and increased lifespan by ROS scavenging and interference with the serotonin system. Hence, WA may serve as promising candidate to treat depression.

Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/drug effects , Longevity/drug effects , Receptors, Serotonin/genetics , Withanolides/pharmacology , Animals , Caenorhabditis elegans/physiology , Fluoxetine/pharmacology , Gene Knockout Techniques , Molecular Docking Simulation , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Receptors, Serotonin/metabolism , Withania/chemistry