Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans

Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson’s disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.

Download Full-text

Ingredients in Zijuan Pu’er Tea Extract Alleviate β-Amyloid Peptide Toxicity in a Caenorhabditis elegans Model of Alzheimer’s Disease Likely through DAF-16

Molecules ◽

10.3390/molecules24040729 ◽

2019 ◽

Vol 24 (4) ◽

pp. 729 ◽

Cited By ~ 2

Author(s):

Fangzhou Du ◽

Lin Zhou ◽

Yan Jiao ◽

Shuju Bai ◽

Lu Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Caenorhabditis Elegans ◽

Protective Effect ◽

Nuclear Translocation ◽

Amyloid Β ◽

Amyloid Peptide ◽

C Elegans ◽

Β Amyloid

Amyloid-β, one of the hallmarks of Alzheimer’s disease (AD), is toxic to neurons and can also cause brain cell death. Oxidative stress is known to play an important role in AD, and there is strong evidence that oxidative stress is associated with amyloid-β. In the present study we report the protective effect of Zijuan Pu’er tea water extract (ZTWE) and the mixture of main ingredients (+)-catechins, caffeine and procyanidin (MCCP) in ZTWE on β-amyloid-induced toxicity in transgenic Caenorhabditis elegans (C. elegans) CL4176 expressing the human Aβ1–42 gene. ZTWE, (+)-catechins, caffeine, procyanidin and MCCP delayed the β-amyloid-induced paralysis to different degrees. The MCCP treatment did not affect the transcript abundance of amyloid-β transgene (amy-1); however, Thioflavin T staining showed a significant decrease in Aβ accumulation compared to untreated worms. Further research using transgenic worms found that MCCP promoted the translocation of DAF-16 from cytoplasm to nucleus and increased the expression of superoxide dismutase 3 (SOD-3). In addition, MCCP decreased the reactive oxygen species (ROS) content and increased the SOD activity in CL4176 worms. In conclusion, the results suggested that MCCP had a significant protective effect on β-amyloid-induced toxicity in C. elegans by reducing β-amyloid aggregation and inducing DAF-16 nuclear translocation that could activate the downstream signal pathway and enhance resistance to oxidative stress.

Download Full-text

Mutations in C. elegans neuroligin-like glit-1, the apoptosis pathway and the calcium chaperone crt-1 increase dopaminergic neurodegeneration after 6-OHDA treatment

10.1101/203067 ◽

2017 ◽

Author(s):

Sarah-Lena Offenburger ◽

Elisabeth Jongsma ◽

Anton Gartner

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Death ◽

Dopaminergic Neurons ◽

Apoptosis Pathway ◽

C Elegans ◽

Dopaminergic Neurodegeneration ◽

Cell Death Pathway ◽

6 Hydroxydopamine

AbstractThe loss of dopaminergic neurons is a hallmark of Parkinson’s disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative- stress inducing drug that is specifically taken up into dopaminergic neurons. Furthermore, glit-1 mutants exhibit increased sensitivity to oxidative stress induced by H2O2 and paraquat. We provide evidence that GLIT-1 acts in the same genetic pathway as the previously identified tetraspanin TSP-17. After exposure to 6-OHDA and paraquat, glit-1 and tsp-17 mutants show almost identical, non-additive hypersensitivity phenotypes and exhibit highly increased induction of oxidative stress reporters. TSP-17 and GLIT-1 are both expressed in dopaminergic neurons. In addition, the neuroligin-like GLIT-1 is expressed in pharynx, intestine and several unidentified cells in the head. GLIT-1 is homologous, but not orthologous to neuroligins, transmembrane proteins required for the function of synapses. The Drosophila GLIT-1 homologue Gliotactin in contrast is required for epithelial junction formation. We report that GLIT-1 likely acts in multiple tissues to protect against 6-OHDA, and that the epithelial barrier of C. elegans glit-1 mutants does not appear to be compromised. We further describe that hyperactivation of the SKN-1 oxidative stress response pathway alleviates 6-OHDA-induced neurodegeneration. In addition, we find that mutations in the canonical apoptosis pathway and the calcium chaperone crt-1 cause increased 6-OHDA-induced dopaminergic neuron loss. In summary, we report that the neuroligin-like GLIT-1, the canonical apoptosis pathway and the calreticulin CRT-1 are required to prevent 6-OHDA-induced dopaminergic neurodegeneration.Author summaryNeurons use dopamine as a chemical messenger to mediate diverse behaviours. The gradual loss of dopaminergic neurons in specific brain areas is a hallmark of Parkinson’s disease. The increased occurrence of highly reactive oxygen radicals, also called oxidative stress, is assumed to contribute to the demise of dopaminergic neurons. In this study we searched for genes that protect dopaminergic neurons against oxidative stress. We used the nematode C. elegans, a well- characterised model organism whose dopamine signalling system is very similar to that of humans. When C. elegans is exposed to 6-hydroxydopamine, an oxidative stress-inducing compound, dopaminergic neurons gradually die. Our major findings include: (i) absence of the neuroligin-like gene glit-1 causes highly increased cell death of dopaminergic neurons after 6-OHDA exposure; (ii) GLIT-1 acts in a similar manner as the previously identified tetraspanin TSP-17; (iii) GLIT-1 and TSP-17 also protect C. elegans from other types of oxidative stress; and (iv) the programmed cell death pathway and a calcium chaperone protect dopaminergic neurons as well. Collectively, this study shows that apoptosis proteins, the calcium chaperone CRT-1 and the neuroligin-like GLIT-1 protect against neurodegeneration after oxidative stress exposure.

Download Full-text

Streblus asper Lour. exerts MAPK and SKN-1 mediated anti-aging, anti-photoaging activities and imparts neuroprotection by ameliorating Aβ in Caenorhabditis elegans

Nutrition and Healthy Aging ◽

10.3233/nha-210121 ◽

2021 ◽

pp. 1-17

Author(s):

Mani Iyer Prasanth ◽

James Michael Brimson ◽

Dicson Sheeja Malar ◽

Anchalee Prasansuklab ◽

Tewin Tencomnao

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Stress Resistance ◽

Vital Role ◽

Transgenic Strain ◽

Wild Type ◽

Neuroprotective Effects ◽

C Elegans ◽

Streblus Asper

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.

Download Full-text

Protective effect of Annona crassiflora on oxidative stress and Alzheimer’s models in Caenorhabditis elegans

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2018.10.307 ◽

2018 ◽

Vol 128 ◽

pp. S125

Author(s):

Edson Lucas dos Santos ◽

Natasha Leite ◽

Laura Costa Alves de Araújo ◽

José Tarcisio Giffoni de Carvalho ◽

Kely de Picoli Souza

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Protective Effect ◽

Annona Crassiflora

Download Full-text

Secoisolariciresinol Diglucoside Delays the Progression of Aging-Related Diseases and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1293935 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Min Lu ◽

Lin Tan ◽

Xiao-Gang Zhou ◽

Zhong-Lin Yang ◽

Qing Zhu ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Body Movement ◽

Mrna Level ◽

Secoisolariciresinol Diglucoside ◽

Neuroprotective Effects ◽

Sesame Seeds ◽

C Elegans ◽

Age Related ◽

6 Hydroxydopamine ◽

And Oxidative Stress

Secoisolariciresinol diglucoside (SDG) is a phytoestrogen and rich in food flaxseed, sunflower seeds, and sesame seeds. Among the beneficial pharmacological activities of SDG on health, many are age related, such as anticancer, antidiabetes, antioxidant, and neuroprotective effects. Thus, we investigated if SDG had an effect on antiaging in Caenorhabditis elegans (C. elegans). Our results showed that SDG could extend the lifespan of C. elegans by up to 22.0%, delay age-related decline of body movement, reduce the lethality of heat and oxidative stress, alleviate dopamine neurodegeneration induced by 6-hydroxydopamine (6-OHDA), and decrease the toxicity of Aβ protein in C. elegans. SDG could increase the expression of the downstream genes of DAF-16, DAF-12, NHR-80, and HSF-1 at mRNA level. SDG could not extend the lifespan of mutants from genes daf-16, hsf-1, nhr-80, daf-12, glp-1, eat-2, and aak-2. The above results suggested that SDG might enhance the stress resistance, delay the progression of aging-related diseases, and extend the lifespan of C. elegans via DAF-16 and HSF-1.

Download Full-text

Lipopolysaccharide exposure induces oxidative damage in Caenorhabditis elegans: protective effects of carnosine

BMC Pharmacology and Toxicology ◽

10.1186/s40360-020-00455-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Jing Ma ◽

Xiaoyuan Xu ◽

Ranran Wang ◽

Haijing Yan ◽

Huijuan Yao ◽

...

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Signaling Pathway ◽

P38 Mapk ◽

Mapk Signaling ◽

Protective Effects ◽

Related Gene ◽

Rt Pcr ◽

C Elegans ◽

Apoptosis Related Gene

Abstract Background The present study was designed to investigate the protective effects and mechanisms of carnosine on lipopolysaccharide (LPS)-induced injury in Caenorhabditis elegans. Methods C. elegans individuals were stimulated for 24 h with LPS (100 μg/mL), with or without carnosine (0.1, 1, 10 mM). The survival rates and behaviors were determined. The activities of superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) were determined using the respective kits. Reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the differential expression of sod-1, sod-2, sod-3, daf-16, ced-3, ced-9, sek-1, and pmk-1. Western blotting was used to determine the levels of SEK1, p38 mitogen-activated protein kinase (MAPK), cleaved caspase3, and Bcl-2. C. elegans sek-1 (km2) mutants and pmk-1 (km25) mutants were used to elucidate the role of the p38 MAPK signaling pathway. Results Carnosine improved the survival of LPS-treated C. elegans and rescued behavioral phenotypes. It also restrained oxidative stress by decreasing MDA levels and increasing SOD, GR, CAT, and GSH levels. RT-PCR results showed that carnosine treatment of wild-type C. elegans up-regulated the mRNA expression of the antioxidant-related genes sod-1, sod-2, sod-3, and daf-16. The expression of the anti-apoptosis-related gene ced-9 and apoptosis-related gene ced-3 was reversed by carnosine. In addition, carnosine treatment significantly decreased cleaved caspase3 levels and increased Bcl-2 levels in LPS-treated C. elegans. Apoptosis in the loss-of-function strains of the p38 MAPK signaling pathway was suppressed under LPS stress; however, the apoptotic effects of LPS were blocked in the sek-1 and pmk-1 mutants. The expression levels of sek-1 and pmk-1 mRNAs were up-regulated by LPS and reversed by carnosine. Finally, the expression of p-p38MAPK and SEK1 was significantly increased by LPS, which was reversed by carnosine. Conclusion Carnosine treatment protected against LPS injury by decreasing oxidative stress and inhibiting apoptosis through the p38 MAPK pathway.

Download Full-text

Caenorhabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals

Molecules ◽

10.3390/molecules25143194 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3194

Author(s):

Begoña Ayuda-Durán ◽

Susana González-Manzano ◽

Ana M. González-Paramás ◽

Celestino Santos-Buelga

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Model Organism ◽

Lipid Peroxides ◽

Biological Research ◽

Loss Of Function ◽

Fluorescent Reporters ◽

C Elegans ◽

High Degree

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 pathways regulating oxidative stress in C. elegans are discussed, as well as the methodological approaches used for their evaluation in the worm. In particular, the following aspects are reviewed: the use of stress assays, determination of chemical and biochemical markers (e.g., ROS, carbonylated proteins, lipid peroxides or altered DNA), influence on gene expression and the employment of mutant worm strains, either carrying loss-of-function mutations or fluorescent reporters, such as the GFP.

Download Full-text

The DM Domain Transcription Factor MAB-3 Regulates Male Hypersensitivity to Oxidative Stress in Caenorhabditis elegans

Molecular and Cellular Biology ◽

10.1128/mcb.01459-09 ◽

2010 ◽

Vol 30 (14) ◽

pp. 3453-3459 ◽

Cited By ~ 8

Author(s):

Hideki Inoue ◽

Eisuke Nishida

Keyword(s):

Oxidative Stress ◽

Transcription Factor ◽

Caenorhabditis Elegans ◽

Sex Determination ◽

Target Genes ◽

Stress Sensitivity ◽

Gata Factor ◽

X Chromosomes ◽

C Elegans ◽

Dm Domain

ABSTRACT Sex differences occur in most species and involve a variety of biological characteristics. The nematode Caenorhabditis elegans consists of two sexes, self-fertile hermaphrodites (XX) and males (XO). Males differ from hermaphrodites in morphology, behavior, and life span. Here, we find that male C. elegans worms are much more sensitive than hermaphrodites to oxidative stress and show that the DM domain transcription factor MAB-3 plays a pivotal role in determining this male hypersensitivity. The hypersensitivity to oxidative stress does not depend on the dosage of X chromosomes but is determined by the somatic sex determination pathway. Our analyses show that the male hypersensitivity is controlled by MAB-3, one of the downstream effectors of the master terminal switch TRA-1 in the sex determination pathway. Moreover, we find that MAB-3 suppresses expression of several transcriptional target genes of the ELT-2 GATA factor, which is a global regulator of transcription in the C. elegans intestine, and show that RNA interference (RNAi) against elt-2 increases sensitivity to oxidative stress. These results strongly suggest that the DM domain protein MAB-3 regulates oxidative stress sensitivity by repressing transcription of ELT-2 target genes in the intestine.

Download Full-text

Caenorhabditis elegans to Model the Capacity of Ascorbic Acid to Reduce Acute Nitrite Toxicity under Different Feed Conditions: Multivariate Analytics on Behavioral Imaging

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18042068 ◽

2021 ◽

Vol 18 (4) ◽

pp. 2068

Author(s):

Samuel Verdu ◽

Alberto J. Perez ◽

Conrado Carrascosa ◽

José M. Barat ◽

Pau Talens ◽

...

Keyword(s):

Ascorbic Acid ◽

Caenorhabditis Elegans ◽

Protective Effect ◽

Animal Health ◽

Biological Systems ◽

Meat Products ◽

Processed Meat ◽

Multivariate Statistical ◽

C Elegans ◽

Nitrite Toxicity

Nitrocompounds are present in the environment and human diet and form part of vegetables and processed meat products as additives. These compounds are related to negative impacts on human and animal health. The protective effect of ascorbic acid has been demonstrated by some biological systems as regards several nitrocompounds. This work focused on studying the possibility of modeling this effect on nitrite toxicity with the model Caenorhabditis elegans. The three factors studied in this work were ascorbic acid concentration, nitrite exposure concentration, and presence/absence of food. The protective effect was evaluated by scoring lethality and its impact on behavior by means of multivariate statistical methods and imaging analytics. The effects of nitrite and the influence of food availability were evidenced. Apart from increasing lethality, nitrite had disruption effects on movements. All the observed symptoms reduced when ascorbic acid was administered, and it diminished lethality in all cases. Ascorbic acid maintained nematodes’ postural capacities. The results suggest that nitrites’ nonspecific toxicity in C. elegans can be mitigated by ascorbic acid, as previously evidenced in other biological systems. Thus, our results reveal the ability of C. elegans to reproduce the known protective effect of ascorbic acid against nitrite.

Download Full-text

Mulberry Anthocyanin Extract Ameliorates Oxidative Damage in HepG2 Cells and Prolongs the Lifespan of Caenorhabditis elegans through MAPK and Nrf2 Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7956158 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 19

Author(s):

Fujie Yan ◽

Yushu Chen ◽

Ramila Azat ◽

Xiaodong Zheng

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Hepg2 Cells ◽

Insulin Signalling ◽

Glucose Consumption ◽

Redox Status ◽

C Elegans ◽

Beneficial Effects

Mulberry anthocyanins possess many pharmacological effects including liver protection, anti-inflammation, and anticancer. The aim of this study was to evaluate whether mulberry anthocyanin extract (MAE) exerts beneficial effects against oxidative stress damage in HepG2 cells and Caenorhabditis elegans. In vitro, MAE prevented cytotoxicity, increased glucose consumption and uptake, and eliminated excessive intracellular free radicals in H2O2-induced cells. Moreover, MAE pretreatment maintained Nrf2, HO-1, and p38 MAPK stimulation and abolished upregulation of p-JNK, FOXO1, and PGC-1α that were involved in oxidative stress and insulin signalling modulation. In vivo, extended lifespan was observed in C. elegans damaged by paraquat in the presence of MAE, while these beneficial effects were disappeared in pmk-1 and daf-16 mutants. PMK-1 and SKN-1 were activated after exposure to paraquat and MAE suppressed PMK-1 activation but enhanced SKN-1 stimulation. Our findings suggested that MAE recovered redox status in HepG2 cells and C. elegans that suffered from oxidative stress, which might be by targeting MAPKs and Nrf2.

Download Full-text