scholarly journals Neuroprotective Effects of Palmatine via the Enhancement of Antioxidant Defense and Small Heat Shock Protein Expression in Aβ-Transgenic Caenorhabditis elegans

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Weizhang Jia ◽  
Qina Su ◽  
Qiong Cheng ◽  
Qiong Peng ◽  
Aimin Qiao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Caenorhabditis Elegans ◽  
Radical Scavenging ◽  
Amyloid Β ◽  
Small Heat Shock Protein ◽  
Isoquinoline Alkaloid ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Aβ Aggregation

Palmatine is a naturally occurring isoquinoline alkaloid that has been reported to display neuroprotective effects against amyloid-β- (Aβ-) induced neurotoxicity. However, the mechanisms underlying the neuroprotective activities of palmatine remain poorly characterized in vivo. We employed transgenic Caenorhabditis elegans models containing human Aβ1-42 to investigate the effects and possible mechanisms of palmatine-mediated neuroprotection. Treatment with palmatine significantly delayed the paralytic process and reduced the elevated reactive oxygen species levels in Aβ-transgenic C. elegans. In addition, it increased oxidative stress resistance without affecting the lifespan of wild-type C. elegans. Pathway analysis suggested that the differentially expressed genes were related mainly to aging, detoxification, and lipid metabolism. Real-time PCR indicated that resistance-related genes such as sod-3 and shsp were significantly upregulated, while the lipid metabolism-related gene fat-5 was downregulated. Further studies demonstrated that the inhibitory effects of palmatine on Aβ toxicity were attributable to the free radical-scavenging capacity and that the upregulated expression of resistance-related genes, especially shsp, whose expression was regulated by HSF-1, played crucial roles in protecting cells from Aβ-induced toxicity. The research showed that there were significantly fewer Aβ deposits in transgenic CL2006 nematodes treated with palmatine than in control nematodes. In addition, our study found that Aβ-induced toxicity was accompanied by dysregulation of lipid metabolism, leading to excessive fat accumulation in Aβ-transgenic CL4176 nematodes. The alleviation of lipid disorder by palmatine should be attributed not only to the reduction in fat synthesis but also to the inhibition of Aβ aggregation and toxicity, which jointly maintained metabolic homeostasis. This study provides new insights into the in vivo neuroprotective effects of palmatine against Aβ aggregation and toxicity and provides valuable targets for the prevention and treatment of AD.

scholarly journals Antioxidant Activities and Reduced Amyloid-β Toxicity of 7-Hydroxycalamenene Isolated from the Essential Oil of Zelkova serrata Heartwood

2016 ◽  
Vol 11 (9) ◽  
pp. 1934578X1601100
Author(s):  
Pei-Ling Yen ◽  
Sen-Sung Cheng ◽  
Chia-Cheng Wei ◽  
Huan-You Lin ◽  
Vivian Hsiu-Chuan Liao ◽  
...  
Keyword(s):  
Essential Oil ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Amyloid Β ◽  
Total Phenolic ◽  
C Elegans ◽  
In Vivo Assays ◽  
Zelkova Serrata

The in vitro and in vivo antioxidant activities and its potential to protect against amyloid-β toxicity of essential oils from Zelkova serrata (Thunb.) Makino were investigated in the model organism Caenorhabditis elegans. The results revealed that the essential oil of Z. serrata heartwood exhibited great radical scavenging activities and high total phenolic content. In vivo assays showed significant inhibition of oxidative damage in wild-type C. elegans under juglone-induced oxidative stress and heat shock. Based on results from both in vitro and in vivo assays, the major compound in essential oil of heartwood, (-)-(1 S, 4 S)-7-hydroxycalamenene (1 S, 4 S-7HC), may contribute significantly to the observed antioxidant activity. Further evidence showed that 1 S, 4 S-7HC significantly delayed the paralysis phenotype in amyloid beta-expressing transgenic C. elegans. These findings suggest that 1 S, 4 S-7HC from the essential oil of Z. serrata heartwood has potential as a source for antioxidant or Alzheimer's disease treatment.

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

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 192 ◽  
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.

scholarly journals Protective Effect and Mechanism of Fruit Extract of Aegle marmelos Against Amyloid-β Toxicity in a Transgenic Caenorhabditis elegans

2020 ◽  
Vol 15 (7) ◽  
pp. 1934578X2093351
Author(s):  
Roongpetch Keowkase ◽  
Nattanon Kijmankongkul ◽  
Wanapong Sangtian ◽  
Sireethorn Poomborplab ◽  
Chatpiti Santa-ardharnpreecha ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Amyloid Β ◽  
The Elderly ◽  
Potential Candidate ◽  
Aegle Marmelos ◽  
Antioxidative Effect ◽  
Fruit Extract ◽  
Aβ Oligomers ◽  
C Elegans

Alzheimer’s disease (AD) is the most common form of dementia found in the elderly. AD is caused by the accumulation of toxic proteins including amyloid-β (Aβ). The purpose of this study was to investigate the effect of fruit extract of Aegle marmelos against Aβ toxicity in Caenorhabditis elegans. The fruit of A. marmelos has been used in a traditional Thai herb formula in fatigue patients recovering from illnesses such as fever and diarrhea. We used a transgenic C. elegans strain CL4176, which expresses the human Aβ42, to investigate the effects and the mechanisms of action of the extracts against Aβ toxicity. The extract of A. marmelos significantly delayed Aβ-induced paralysis. Aegle marmelos lost the ability to delay Aβ-induced paralysis in worms fed with daf-16 ribonucleic acid interference (RNAi) bacteria, but not in worms fed with hsf-1 and skin-1 RNAi bacteria. These results indicated that daf-16 transcription factor was required for A. marmelos-mediated delayed paralysis. Aegle marmelos enhanced the level of daf-16 gene. Taken together, these results indicated that A. marmelos reduced Aβ toxicity via the DAF-16-mediated cell signaling pathway. In addition, A. marmelos reduced toxic Aβ oligomers. Aegle marmelos also displayed antioxidative effect in in vivo as it enhanced resistance to paraquat-induced oxidative stress in wild type worms. All of the results suggested that A. marmelos can protect against Aβ-induced toxicity and can be a potential candidate for the prevention or treatment of AD.

scholarly journals Evaluation of antioxidant and neuroprotective activities of Cassia fistula (L.) using the Caenorhabditis elegans model

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5159 ◽  
Author(s):  
Sara Thabit ◽  
Heba Handoussa ◽  
Mariana Roxo ◽  
Nesrine S. El Sayed ◽  
Bruna Cestari de Azevedo ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Caenorhabditis Elegans ◽  
Natural Antioxidants ◽  
Neuroprotective Activity ◽  
Cassia Fistula ◽  
Neuroprotective Effects ◽  
Tropical Asia ◽  
C Elegans

Background Cassia fistula (L.) (Fabaceae) is a medicinal plant from tropical Asia. It is known for its marked antioxidant activity, which is attributed to its high phenolic content. The present study aims at testing both the antioxidant and neuroprotective effects of a hydroalcoholic extract from the aerial parts of Cassia fistula using the Caenorhabditis elegans model, which is widely used in this context. Methods Chemical profiling of secondary metabolites that seem to be responsible for both antioxidant and neuroprotective capacities was carried out by HPLC/PDA/ESI-MSn. Antioxidant activity was tested in vitro by CUPRAC and DPPH assays. In vivo antioxidant and neuroprotective activities were investigated using the C. elegans model. Results The Cassia extract improved the survival rate of the nematodes and protected them against oxidative stress. In addition, a decrease in the accumulation of reactive oxygen species (ROS) was observed. The important role of DAF-16/FOXO pathway was confirmed through an increased nuclear localization of the DAF-16 transcription factor, increased expression of SOD-3 stress response gene and decreased expression of HSP-16.2. Furthermore, the putative involvement of SKN-1/NRF2 pathway was demonstrated by a decrease in GST-4 levels. A neuroprotective activity of the Cassia extract was shown by a decline in polyglutamine (polyQ40) aggregate formation and a delay in paralysis caused by amyloid beta (Aβ1–42) accumulation. Discussion The Cassia extract exhibits substantial antioxidant and neuroprotective activities in vivo, which might provide a rich and novel source of natural antioxidants and neuroprotective compounds to be further studied for the use in various food and cosmetic industrial fields.

In silico and In vivo Evaluation of Oxidative Stress Inhibitors Against Parkinson`s Disease using the C. elegans Model

2020 ◽  
Vol 23 (8) ◽  
pp. 814-826
Author(s):  
Pradeep Hanumanthappa ◽  
Arpitha Ashok ◽  
Inderjit Prakash ◽  
Carmel I. Priya ◽  
Julie Zinzala ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Neurodegenerative Disorder ◽  
In Vivo Evaluation ◽  
Neuroprotective Effects ◽  
Ample Evidence ◽  
C Elegans ◽  
Rational Drug ◽  
Cullin 3 ◽  
Anti Oxidant

Background: Parkinson’s disease ranks second, after Alzheimer’s as the major neurodegenerative disorder, for which no cure or disease-modifying therapies exist. Ample evidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to neuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases involving damaged anti-oxidative machinery. Objective: The design of target specific inhibitors for the Cullin-3 protein might be a promising strategy to increase the Nrf2 levels and to decrease the possibility of “off-target” toxic properties. Methods: In the present study, an integrated computational and wet lab approach was adopted to identify small molecule inhibitors for Cullin-3. The rational drug designing process comprised homology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc natural compound database, molecular docking and Molecular dynamics based screening of ligand molecules. In vivo validations of an identified lead compound were conducted in the PD model of C. elegans. Results and Discussion: Our strategy yielded a potential inhibitor; (Glide score = -12.31), which was evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able to efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects were attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase, catalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the Cullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans. Conclusion: Taken together, these findings highlight the potential utility of Cullin-3 inhibition to block the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism of action would be interesting.

Berberine nanoencapsulation attenuates hallmarks of scoplomine induced Alzheimer's-like disease in rats

2020 ◽  
Vol 15 ◽  
Author(s):  
Samar R. Saleh ◽  
Mariam M. Abady ◽  
Mohammed Nofal ◽  
Nashwa W. Yassa ◽  
Mohamed S. Abdel-latif ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Histopathological Examination ◽  
Memory Function ◽  
Amyloid Β ◽  
Active Pharmaceutical Ingredient ◽  
Isoquinoline Alkaloid ◽  
Drug Uptake ◽  
Male Rats ◽  
Morris Water Maze Test ◽  
Neuroprotective Effects

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, antiinflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. Methods: BBR-NPs were formulated using ionic gelation method and tripolyphosphate was chosen as a cross linker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty six Wistar male rats were randomly distributed into: three control groups, received saline, polyethylene glycol or chitosan- NPs respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates as well as neuroplasticity markers and histopathological examination were assessed. Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands toward AChE and Aβ42 formation and significantly down regulated Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. Conclusions: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake which need more investigation in future work.

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

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.

scholarly journals Caenorhabditis elegans as an in vivo Model to Assess Amphetamine Tolerance

2021 ◽  
pp. 1-9
Author(s):  
Dayana Torres Valladares ◽  
Sirisha Kudumala ◽  
Murad Hossain ◽  
Lucia Carvelli
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Genetic Model ◽  
In Vivo Model ◽  
C Elegans ◽  
Hyperactivity Disorder ◽  
In Vitro Data

Amphetamine is a potent psychostimulant also used to treat attention deficit/hyperactivity disorder and narcolepsy. In vivo and in vitro data have demonstrated that amphetamine increases the amount of extra synaptic dopamine by both inhibiting reuptake and promoting efflux of dopamine through the dopamine transporter. Previous studies have shown that chronic use of amphetamine causes tolerance to the drug. Thus, since the molecular mechanisms underlying tolerance to amphetamine are still unknown, an animal model to identify the neurochemical mechanisms associated with drug tolerance is greatly needed. Here we took advantage of a unique behavior caused by amphetamine in <i>Caenorhabditis elegans</i> to investigate whether this simple, but powerful, genetic model develops tolerance following repeated exposure to amphetamine. We found that at least 3 treatments with 0.5 mM amphetamine were necessary to see a reduction in the amphetamine-induced behavior and, thus, to promote tolerance. Moreover, we found that, after intervals of 60/90 minutes between treatments, animals were more likely to exhibit tolerance than animals that underwent 10-minute intervals between treatments. Taken together, our results show that <i>C. elegans</i> is a suitable system to study tolerance to drugs of abuse such as amphetamines.

Neuroprotective Effects of the FGF21 Analogue LY2405319

2021 ◽  
pp. 1-13
Author(s):  
Claire Rühlmann ◽  
David Dannehl ◽  
Marcus Brodtrück ◽  
Andrew C. Adams ◽  
Jan Stenzel ◽  
...  
Keyword(s):  
Glial Cells ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Fibroblast Growth Factor 21 ◽  
Neuroprotective Effects ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures ◽  
Abca1 Mrna

Background: To date, there are no effective treatments for Alzheimer’s disease (AD). Thus, a significant need for research of therapies remains. Objective: One promising pharmacological target is the hormone fibroblast growth factor 21 (FGF21), which is thought to be neuroprotective. A clinical candidate for medical use could be the FGF21 analogue LY2405319 (LY), which has a specificity and potency comparable to FGF21. Methods: The present study investigated the potential neuroprotective effect of LY via PPARγ/apoE/abca1 pathway which is known to degrade amyloid-β (Aβ) plaques by using primary glial cells and hippocampal organotypic brain slice cultures (OBSCs) from 30- and 50-week-old transgenic APPswe/PS1dE9 (tg) mice. By LY treatment of 52-week-old tg mice with advanced Aβ deposition, we further aimed to elaborate the effect of LY on AD pathology in vivo. Results: LY application to primary glial cells caused an upregulation of pparγ, apoE, and abca1 mRNA expression and significantly decreased number and area of Aβ plaques in OBSCs. LY treatment in tg mice increased cerebral [18F] FDG uptake and N-acetylaspartate/creatine ratio indicating enhanced neuronal activity and integrity. Although LY did not reduce the number of Aβ plaques in tg mice, the number of iba1-positive cells was significantly decreased indicating reduced microgliosis. Conclusion: These data identified LY in vitro as an activator of Aβ degrading genes leading to cerebral Aβ load amelioration in early and late AD pathology. Although Aβ plaque reduction by LY failed in vivo, LY may be used as therapeutic agent to treat AD-related neuroinflammation and impaired neuronal integrity.

Transfer and tissue-specific accumulation of components in embryos of Caenorhabditis elegans and dolichura: in vivo analysis with a low-cost signal

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 317-330 ◽  
Author(s):  
O. Bossinger ◽  
E. Schierenberg
Keyword(s):  
Caenorhabditis Elegans ◽  
Low Cost ◽  
Free Living ◽  
Tissue Specific ◽  
C Elegans ◽  
Specific Accumulation ◽  
In Vivo Analysis

The pattern of autofluorescence in the two free-living namatodes Rhabditis dolichura and Caenorhabditis compared. In C. elegans, during later embryogenesis cells develop a typical bluish autofluorescence as illumination, while in Rh. dolichura a strong already present in the unfertilized egg. Using a new,

Sign in / Sign up

Export Citation Format

Share Document