Abstract:The nematode Caenorhabditis elegans was introduced as a model organism in biological research by Sydney Brenner in the 1970s. Since then, it has been increasingly used for investigating processes such as ageing, oxidative stress, neurodegeneration, or inflammation, for which there is a high degree of homology between C. elegans and human pathways, so that the worm offers promising possibilities to study mechanisms of action and effects of phytochemicals of foods and plants. In this paper, the genes and pathway… Show more
“…This nematode has a short lifespan and is well suited for experiments. C. elegans is widely used as an animal model for the study of oxidative stress, aging, longevity and neurodegenerative diseases [ 17 , 18 ].…”
Despite the Tiger Milk Mushroom Lignosus rhinocerus (LR) having been used as a traditional medicine, little is known about the neuroprotective effects of LR extracts. This study aims to investigate the neuroprotective effect of three extracts of LR against glutamate-induced oxidative stress in mouse hippocampal (HT22) cells as well as to determine their effect in Caenorhabditis elegans. In vitro, we assessed the toxicity of three LR extracts (ethanol extract (LRE), cold-water extract (LRC) and hot-water extract (LRH)) and their protective activity by MTT assay, Annexin V-FITC/propidium iodide staining, Mitochondrial Membrane Potential (MMP) and intracellular ROS accumulation. Furthermore, we determined the expression of antioxidant genes (catalase (CAT), superoxide dismutase (SOD1 and SOD2) and glutathione peroxidase (GPx)) by qRT-PCR. In vivo, we investigated the neuroprotective effect of LRE, not only against an Aβ-induced deficit in chemotaxis behavior (Alzheimer model) but also against PolyQ40 formation (model for Morbus Huntington) in transgenic C. elegans. Only LRE significantly reduced both apoptosis and intracellular ROS levels and significantly increased the expression of antioxidant genes after glutamate-induced oxidative stress in HT22 cells. In addition, LRE significantly improved the Chemotaxis Index (CI) in C. elegans and significantly decreased PolyQ40 aggregation. Altogether, the LRE exhibited neuroprotective properties both in vitro and in vivo.
“…This nematode has a short lifespan and is well suited for experiments. C. elegans is widely used as an animal model for the study of oxidative stress, aging, longevity and neurodegenerative diseases [ 17 , 18 ].…”
Despite the Tiger Milk Mushroom Lignosus rhinocerus (LR) having been used as a traditional medicine, little is known about the neuroprotective effects of LR extracts. This study aims to investigate the neuroprotective effect of three extracts of LR against glutamate-induced oxidative stress in mouse hippocampal (HT22) cells as well as to determine their effect in Caenorhabditis elegans. In vitro, we assessed the toxicity of three LR extracts (ethanol extract (LRE), cold-water extract (LRC) and hot-water extract (LRH)) and their protective activity by MTT assay, Annexin V-FITC/propidium iodide staining, Mitochondrial Membrane Potential (MMP) and intracellular ROS accumulation. Furthermore, we determined the expression of antioxidant genes (catalase (CAT), superoxide dismutase (SOD1 and SOD2) and glutathione peroxidase (GPx)) by qRT-PCR. In vivo, we investigated the neuroprotective effect of LRE, not only against an Aβ-induced deficit in chemotaxis behavior (Alzheimer model) but also against PolyQ40 formation (model for Morbus Huntington) in transgenic C. elegans. Only LRE significantly reduced both apoptosis and intracellular ROS levels and significantly increased the expression of antioxidant genes after glutamate-induced oxidative stress in HT22 cells. In addition, LRE significantly improved the Chemotaxis Index (CI) in C. elegans and significantly decreased PolyQ40 aggregation. Altogether, the LRE exhibited neuroprotective properties both in vitro and in vivo.
“…To further investigate a potential antioxidant activity of LRE, LRC, and LRH in vivo, C. elegans was employed as a model organism and E. coli OP50 was supplied as a food source [19]. C. elegans is widely used as a model for anti-aging, antioxidant, and longevity research, because it shares high homology with mammalian and human genes and biochemical pathways [18,46,47]. Juglone, a yellow pigment from Juglans regia is commonly used for inducing oxidative stress in C. elelgans, leading to increased intracellular ROS and death [1,48].…”
Section: Discussionmentioning
confidence: 99%
“…Caenorhabditis elegans, a free-living soil nematode, is widely used as a model to investigate aging, stress resistance, neurodegenerative diseases, and longevity because there is high homology between mammalian and human genes [17,18]. The two major signaling pathways that regulate longevity and stress resistance in this nematode are the DAF-16/FOXO and SKN-1/NRF-2 pathways [19].…”
The tiger milk mushroom, Lignosus rhinocerus (LR), exhibits antioxidant properties, as shown in a few in vitro experiments. The aim of this research was to study whether three LR extracts exhibit antioxidant activities in Caenorhabditis elegans. In wild-type N2 nematodes, we determined the survival rate under oxidative stress caused by increased intracellular ROS concentrations. Transgenic strains, including TJ356, TJ375, CF1553, CL2166, and LD1, were used to detect the expression of DAF-16, HSP-16.2, SOD-3, GST-4, and SKN-1, respectively. Lifespan, lipofuscin, and pharyngeal pumping rates were assessed. Three LR extracts (ethanol, and cold and hot water) protected the worms from oxidative stress and decreased intracellular ROS. The extracts exhibited antioxidant properties through the DAF-16/FOXO pathway, leading to SOD-3 and HSP-16.2 modification. However, the expression of SKN-1 and GST-4 was not changed. All the extracts extended the lifespan. They also reduced lipofuscin (a marker for aging) and influenced the pharyngeal pumping rate (another marker for aging). The extracts did not cause dietary restriction. This novel study provides evidence of the functional antioxidant and anti-aging properties of LR. Further studies must confirm that they are suitable for use as antioxidant supplements.
“…In recent years, the nematode Caenorhabditis elegans has been used as a model organism to study the effects and subjacent molecular mechanisms of action of phenolic compounds, in processes such as oxidative stress, caloric metabolism, or longevity [ 13 ]. In previous studies of our group, different flavonoids, i.e., catechins, quercetin, and their phase II metabolites [ 14 , 15 , 16 ] and polyphenol-rich products [ 17 , 18 , 19 ], have been assessed for their effects on longevity and oxidative stress in C. elegans , demonstrating in general favorable outcomes in both respects.…”
Section: Introductionmentioning
confidence: 99%
“…Furthermore, caffeic acid is found both in free and esterified forms in many types of fruits (berries, kiwis, plums, pears or apples, among others), usually representing more than 75% of total hydroxycinnamic acid content, as well as in high concentrations in coffee [12]. In recent years, the nematode Caenorhabditis elegans has been used as a model organism to study the effects and subjacent molecular mechanisms of action of phenolic compounds, in processes such as oxidative stress, caloric metabolism, or longevity [13]. In previous studies of our group, different flavonoids, i.e., catechins, quercetin, and their phase II metabolites [14][15][16] and polyphenol-rich products [17][18][19], have been assessed for their effects on longevity and oxidative stress in C. elegans, demonstrating in general favorable outcomes in both respects.…”
Caffeic and dihydrocaffeic acid are relevant microbial catabolites, being described as products from the degradation of different phenolic compounds i.e., hydroxycinnamoyl derivatives, anthocyanins or flavonols. Furthermore, caffeic acid is found both in free and esterified forms in many fruits and in high concentrations in coffee. These phenolic acids may be responsible for a part of the bioactivity associated with the intake of phenolic compounds. With the aim of progressing in the knowledge of the health effects and mechanisms of action of dietary phenolics, the model nematode Caenorhabditis elegans has been used to evaluate the influence of caffeic and dihydrocaffeic acids on lifespan and the oxidative stress resistance. The involvement of different genes and transcription factors related to longevity and stress resistance in the response to these phenolic acids has also been explored. Caffeic acid (CA, 200 μM) and dihydrocaffeic acid (DHCA, 300 μM) induced an increase in the survival rate of C. elegans under thermal stress. Both compounds also increased the mean and maximum lifespan of the nematode, compared to untreated worms. In general, treatment with these acids led to a reduction in intracellular ROS concentrations, although not always significant. Results of gene expression studies conducted by RT-qPCR showed that the favorable effects of CA and DHCA on oxidative stress and longevity involve the activation of several genes related to insulin/IGF-1 pathway, such as daf-16, daf-18, hsf-1 and sod-3, as well as a sirtuin gene (sir-2.1).
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