Caenorhabditis elegansas Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organismC. eleganshas gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span inC. elegansintroducing the usability of this model system for pharmacological and toxicological research.

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TSG (2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside) from the Chinese HerbPolygonum multiflorumIncreases Life Span and Stress Resistance ofCaenorhabditis elegans

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/124357 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 26

Author(s):

Christian Büchter ◽

Liang Zhao ◽

Susannah Havermann ◽

Sebastian Honnen ◽

Gerhard Fritz ◽

...

Keyword(s):

Life Span ◽

Stress Resistance ◽

Adult Life ◽

Model Organism ◽

Antioxidative Capacity ◽

Loss Of Function ◽

Polygonum Multiflorum ◽

Adult Life Span ◽

C Elegans ◽

Related Transcription Factor

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) was isolated fromPolygonum multiflorum, a plant which is traditionally used as an anti-ageing drug. We have analysed ageing-related effects of TSG in the model organismC. elegansin comparison to resveratrol. TSG exerted a high antioxidative capacity both in a cell-free assay and in the nematode. The antioxidative capacity was even higher compared to resveratrol. Presumably due to its antioxidative effects, treatment with TSG decreased the juglone-mediated induction of the antioxidative enzyme SOD-3; the induction of the GST-4 by juglone was diminished slightly. TSG increased the resistance ofC. elegansagainst lethal thermal stress more prominently than resveratrol (50 μM TSG increased mean survival by 22.2%). The level of the ageing pigment lipofuscin was decreased after incubation with the compound. TSG prolongs the mean, median, and maximum adult life span ofC. elegansby 23.5%, 29.4%, and 7.2%, respectively, comparable to the effects of resveratrol. TSG-mediated extension of life span was not abolished in a DAF-16 loss-of-function mutant strain showing that this ageing-related transcription factor is not involved in the effects of TSG. Our data show that TSG possesses a potent antioxidative capacity, enhances the stress resistance, and increases the life span of the nematodeC. elegans.

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Agrimonia procera Wallr. Extract Increases Stress Resistance and Prolongs Life Span in Caenorhabditis elegans via Transcription Factor DAF-16 (FoxO Orthologue)

Antioxidants ◽

10.3390/antiox7120192 ◽

2018 ◽

Vol 7 (12) ◽

pp. 192 ◽

Cited By ~ 2

Author(s):

Christina Saier ◽

Inge Gommlich ◽

Volker Hiemann ◽

Sabrina Baier ◽

Karoline Koch ◽

...

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Life Span ◽

Stress Resistance ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Model Organism ◽

Amyloid Β ◽

Ethanol Extract

Agrimonia procera is a pharmacologically interesting plant which is proposed to protect against various diseases due to its high amount of phytochemicals, e.g., polyphenols. However, in spite of the amount of postulated health benefits, studies concerning the mechanistic effects of Agrimonia procera are limited. Using the nematode Caenorhabditis elegans, we were able to show that an ethanol extract of Agrimonia procera herba (eAE) mediates strong antioxidative effects in the nematode: Beside a strong radical-scavenging activity, eAE reduces accumulation of reactive oxygen species (ROS) accumulation and protects against paraquat-induced oxidative stress. The extract does not protect against amyloid-β-mediated toxicity, but efficiently increases the life span (up to 12.7%), as well as the resistance to thermal stress (prolongation of survival up to 22%), of this model organism. Using nematodes deficient in the forkhead box O (FoxO)-orthologue DAF-16, we were able to demonstrate that beneficial effects of eAE on stress resistance and life span were mediated via this transcription factor. We showed antioxidative, stress-reducing, and life-prolonging effects of eAE in vivo and were able to demonstrate a molecular mechanism of this extract. These results may be important for identifying further molecular targets of eAE in humans.

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How Animals Perceive Secondary Plant Compounds

Herbivores: Their Interactions with Secondary Plant Metabolites ◽

10.1016/b978-0-08-092545-5.50008-0 ◽

1992 ◽

pp. 89-134 ◽

Cited By ~ 16

Author(s):

JAMES L. FRAZIER

Keyword(s):

Secondary Plant Compounds ◽

Plant Compounds ◽

Secondary Plant

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Electrophysiological Measures of Aging Pharynx Function in C. elegans Reveal Enhanced Organ Functionality in Older, Long-lived Mutants

The Journals of Gerontology Series A ◽

10.1093/gerona/glx230 ◽

2017 ◽

Vol 74 (8) ◽

pp. 1173-1179 ◽

Cited By ~ 7

Author(s):

Joshua Coulter Russell ◽

Nikolay Burnaevskiy ◽

Bridget Ma ◽

Miguel Arenas Mailig ◽

Franklin Faust ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Heat Shock ◽

Life Span ◽

Insulin Signaling ◽

Model System ◽

Wild Type ◽

Organ Function ◽

C Elegans ◽

Age Related ◽

The Relationship

Abstract The function of the pharynx, an organ in the model system Caenorhabditis elegans, has been correlated with life span and motility (another measure of health) since 1980. In this study, in order to further understand the relationship between organ function and life span, we measured the age-related decline of the pharynx using an electrophysiological approach. We measured and analyzed electropharyngeograms (EPG) of wild type animals, short-lived hsf-1 mutants, and long-lived animals with genetically decreased insulin signaling or increased heat shock pathway signaling; we recorded a total of 2,478 EPGs from 1,374 individuals. As expected, the long-lived daf-2(e1370) and hsf-1OE(uthIs235) animals maintained pharynx function relatively closer to the youthful state during aging, whereas the hsf-1(sy441) and wild type animals’ pharynx function deviated significantly further from the youthful state at advanced age. Measures of the amount of variation in organ function can act as biomarkers of youthful physiology as well. Intriguingly, the long-lived animals had greater variation in the duration of pharynx contraction at older ages.

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