1K Papers found (0.011 seconds)

Pandey R et al. (2010) Seizure "Baccoside A suppresses epileptic-like seizure/convulsion in Caenorhabditis elegans."

Gupta SK, Pandey R, Wolkenhauer O, Vera J, Gupta S, Tandon S

[

Seizure,

2010]

The 1 mm long Caenorhabditis elegans is one of the prime research tools to study different human neurodegenerative diseases. We have considered the case in which increase in the surrounding temperature of this multicellular model leads to abnormal bursts of neuronal cells that can be linked to seizure or convulsion. The induction of such seizure/convulsion mechanism was done by gradually increasing the temperature with 1x buffer (100 mM NaCl, 50 mM MgCl(2)) in adult C. elegans. In the present experiment it is demonstrated that Baccoside A can significantly reduce the seizure/convulsion in C. elegans at higher temperatures (26-28+/-1 degrees C). Furthermore, in T-type Ca(2+) channel cca-1 mutant worms, no convulsion was recorded. Our experimental results suggest that plant molecules from Bacopa monnieri may be useful in suppressing the seizure/convulsion in worms.

Pandey R et al. (2018) Aging (Albany NY) "SIN-3 as a key determinant of lifespan and its sex dependent differential role on healthspan in Caenorhabditis elegans."

Pandey R, Saluja D, Sharma M

[

Aging (Albany NY),

2018]

Aging/senescence includes not just decline in lifespan but also etiologies of age associated morbidities which are inadequately understood. Extensive research has been undertaken to delineate the pathways and generate mutants with extended lifespan. However, little is known about the health status of these long lived mutants in the background of important genetic perturbations. Caenorhabditis elegans is one of the leading in vivo model organisms to study aging. Deletion of SIN-3, a transcription coregulator in C. elegans has been shown to reduce the lifespan of the mutant worms by half as compared to the wild-type and isogenic controls. The current study focuses on the effect of SIN-3 deletion on the healthspan of the worms. We find that not only are sin-3 mutants more susceptible to stress, but the overall stress intolerance and physiological decline is sex dependent. The severity of the phenotype is more pronounced in hermaphrodites as compared to the males carrying the same mutation with respect to the controls. The results further suggest that genetic perturbation along with the gender play an important role in determining the lifespan, healthspan and overall fitness of an organism.

Pandey R et al. (2013) Indian J Exp Biol "Antiaging, antistress and ROS scavenging activity of crude extract of Ocimum sanctum (L.) in Caenorhabditis elegans (Maupas, 1900)."

Shukla V, Pandey R, Tandon S, Gupta S

[

Indian J Exp Biol,

2013]

Since aging is the most important risk factor for variety of diseases, the discovery of a wide range of chemical modulators of aging in model organisms encourages new strategies for targeting age associated diseases. Simple genetic manipulation leads to long-lived and healthy animals, so any compound which could have similar effect would prove a boon to mankind. In the present study, effect of different pharmacological doses (1.0, 0.1, 0.01 and 0.001 mg/mL) of O. sanctum crude extract were used to determine their impact on life span, thermotolerance and ROS scavenging activities in C. elegans. The results revealed that 1 mg/mL of O. sanctum extract significantly extended the life span of C. elegans. The extract also proved to be a strong free radical scavenger and increased resistance against thermal stress. It is also suggested that the protective and life span extending action of the crude extract is not only due to its antioxidant capacity but may also be mediated by modulation of some signaling pathways. Thus, in addition to all the known medicinal property of Ocimum, it is capable of increasing stress tolerance and life span in C. elegans.

Pandey R et al. (2022) Nucleus (Calcutta) "Towards the development of phytoextract based healthy ageing cognitive booster formulation, explored through Caenorhabditis elegans model."

[

Nucleus (Calcutta),

2022]

The positive effect of herbal supplements on aging and age-related disorders has led to the evolution of natural curatives for remedial neurodegenerative diseases in humans. The advancement in aging is exceedingly linked to oxidative stress. Enhanced oxidative stress interrupts health of humans in various ways, necessitating to find stress alleviating herbal resources. Currently, minimal scientifically validated health and cognitive booster resources are available. Therefore, we explored the impact of plant extracts in different combinations on oxidative stress, life span and cognition using the multicellular transgenic humanized C. elegans, and further validated the same in Mus musculus, besides testing their safety and toxicity. In our investigations, the final product-the HACBF (healthy ageing cognitive booster formulation) thus developed was found to reduce major aging biomarkers like lipofuscin, protein carbonyl, lipid levels and enhanced activity of antioxidant enzymes. Further confirmation was done using transgenic worms and RT-PCR. The cognitive boosting activities analyzed in C. elegans and M. musculus model system were found to be at par with donepezil and L-dopa, the two drugs which are commonly used to treat Parkinson's and Alzheimer's diseases. In the transgenic C. elegans model system, the HACBF exhibited reduced aggregation of misfolded disease proteins α-synuclein and increased the health of nicotinic acetylcholine receptor, levels of Acetylcholine and Dopamine contents respectively, the major neurotransmitters responsible for memory, language, learning behavior and movement. Molecular studies clearly indicate that HACBF upregulated major genes responsible for healthy aging and cognitive booster activities in C. elegans and as well as in M. musculus. As such, the present herbal product thus developed may be quite useful for healthy aging and cognitive boosting activities, and more so during this covid-19 pandemic.

Pant A et al. (2016) Exp Gerontol "Corrigendum to "Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans" [Exp. Gerontol. 57 (2014) 81-95]."

Saikia SK, Pant A, Shukla V, Asthana J, Pandey R, Akhoon BA

[

Exp Gerontol,

2016]

The authors would like to acknowledge the contribution of Vikas Mishra for this article.Therefore the correct authorship of this paper at the time should have read as follows:Aakanksha Pant*, Vikas Mishra*, Shilpi K. Saikia, Virendra Shukla, Jyotsna Asthana, Bashir A. Akhoon, Rakesh Pandey.(* authors with equal contribution).The authors would like to apologize for any inconvenience caused.

Pandey, T. et al. (2019) International Worm Meeting "Swertiamarin, a natural secoiridoid glycoside ameliorates dopamine deficit and elicits longevity in Caenorhabditis elegans."

Pandey, R., Pandey, T.

[

International Worm Meeting,

2019]

Ageing is progressive desecration of functional and structural health of the body accompanied by innumerable age-associated neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington's disease. PD is marked with progressive neurodegeneration and motor function decline due to formation of insoluble alpha-synuclein aggregates in the dopaminergic neuron. Dopamine deficiency is the main event underlying the pathophysiology of the PD symptomatology. Here we explored the effect of swertiamarin, a secoiridoid glycoside isolated from Enicostemma littorale Blume (Family-Gentianaceae) for its longevity promoting and anti-parkinsonian activities using Caenorhabditis elegans model system. Our results illustrated that swertiamarin treatment significantly enhanced the oxidative stress tolerance and lifespan in worms, along with alleviation of ageing biomarkers like lipofuscin and protein carbonyl. In agreement with the ameliorated ROS (reactive oxygen species) levels, swertiamarin treatment led to up regulated mRNA expression of antioxidant and phase II detoxification genes viz. sod-3 and gst-4 respectively. Swertiamarin treatment curtailed PD manifestation in terms of reduced ?-synuclein levels and 6-OHDA induced neurodegeneration in transgenic worms. Swertiamarin enhanced dopamine levels in both wild type (N2) and diseased worm (NL5901) as proved from body bend, head thrash and 1-nonanol repulsion assays and LC/MS-MS dopamine content analysis. Altogether, our data suggest that swertiamarin enhanced life span and mitigated PD pathologies in C. elegans. Our studies propose swertiamarin as a potential molecule for its properties against ageing and Parkinson's disease. Keywords: Swertiamarin, Caenorhabditis elegans, reactive oxygen species, ageing, Parkinson's disease, alpha-synuclein

Pant, A. et al. (2017) International Worm Meeting "Eugenol, Xenohormesis and Longevity Promotion."

Pandey, R., Pant, A.

[

International Worm Meeting,

2017]

Aging is a quasi-programmed phenomenon which is universal to all organisms. Understanding the molecular mechanisms regulating aging and age-related diseases is most sought after for designing therapies and interventions for managing age-related mortality and morbidity. Thus, the discovery of age defying natural molecules might cure age-related diseases in humans. Therefore, in an effort to identify safe and effective therapy of natural origin, the present study was designed to evaluate the stress modulatory and lifespan modulating potential of eugenol employing Caenorhabditis elegans model. The Eugenol pre-exposure was found to promote lifespan and alter the stress level in C. elegans in a dose-dependent manner. Therefore, to further unravel the possible genetic mechanism underlying eugenol mediated longevity and stress resistance, the interaction of eugenol with gene regulating these multiple cellular signaling pathways was studied. All of these multiple cellular signaling pathways are highly conserved in Drosophila, Mouse, C. elegans, and Humans. The interaction of eugenol with genes regulating lifespan was deciphered by studying effect of eugenol on gene mutants and gene expression of these genes. The daf-2, daf-16, eat-2, sir-2.1, mev-1, skn-1(zu67) and skn-1(zu135) gene mutants were exposed to eugenol (50 M) and vehicle control. In addition to that knock down of wdr-23 was achieved by RNAi and employed for studying the interaction of eugenol on wdr-23. The eugenol mediated lifespan extension, antiaging effects, stress tolerance and maintenance of healthy lifespan is regulated by multiple cellular signaling pathways. As eugenol treatment failed to augment lifespan of daf-2, eat-2, sir-2.1, skn-1(zu135), skn-1(zu67) and wdr-23 significantly suggesting the involvement of these genes in eugenol mediated stress modulation and lifespan extension. The eugenol exposure was found to mediate DR like effects and xenobiotic stress response in worms which later on modulated insulin/IGF-1 signalling response regulated by master transcription factor DAF-16, SKN-1/NRF pathway regulated by SKN-1, DR like effects, stress response and autophagy by SIR-2.1/SIRTUIN-1 (NAD-dependent deacetylase), P38 MAPK pathway which is regulated by PMK-1, WDR-23/SKN-1 pathway regulated by wdr-23, heat shock response by HSF-1. Altogether, these present study for the first time reports anti-aging and stress modulatory effects of eugenol. These interesting findings highlight the significance of natural molecules in designing therapeutics for managing aging and age-related diseases. Keywords: Aging, Eugenol, Anti-aging, Natural molecules, Xenohormesis, Caenorhabditis elegans

Rathor L et al. (2018) Exp Gerontol "Age-induced diminution of free radicals by Boeravinone B in Caenorhabditis elegans."

Pandey R, Rathor L

[

Exp Gerontol,

2018]

Oxidative damage is accrual of molecular deterioration from reactive oxygen species (ROS) while decrease in generation of ROS is related with free radical scavenging enzymes. Boerhaavia diffusa L. (Nyctaginaceae) derived novel molecule Boeravinone B (BOB) possesses a variety of pharmacological activities, yet their anti-aging potential has not been explored. The aim of the present study was to elucidate the mechanism of BOB mediated oxidative stress resistance and lifespan extension in Caenorhabditis elegans. The results showed that the BOB significantly extends the lifespan of C. elegans with its anti-oxidative potential via reducing accumulation of reactive oxygen species (ROS). BOB was found to recover the shortened lifespan of oxidative stress prone mutants mev-1 and gas-1 (14.75 and 16.11%, respectively). Additionally, this finding supported by the reduced ROS levels seen in BOB treated worms. Further, the effective concentration of BOB (25M) significantly enhanced the expressions of target genes such as superoxide dismutase (SOD-3), glutathione-S-transferase (GST-4) and heat shock protein (HSP-16.2) fused to green fluorescent protein (GFP), and it does so by modulating the stress-related signaling pathways (SEK-1) and transcription factors (SKN-1/Nrf and DAF-16/Foxo). Moreover, BOB exposure (25M) caused significant changes of age-dependent biomarkers such as pharyngeal pumping, body bend, locomotor activity and lipofuscin accumulation were also showed that BOB retards the aging. Overall, the findings highlight the antioxidant supplement triggering pharmaceutical potential of BOB which may serve as a new future perspective for healthy aging or delayed onset of oxidative related diseases.

Srivastava, S. et al. (2017) International Worm Meeting "2-Isopropyl-5-methylphenol ameliorates alpha-synuclein proteotoxicity and intracellular ROS accumulation in Caenorhabditis elegans."

Srivastava, S., Pandey, R.

[

International Worm Meeting,

2017]

Parkinson's disease (PD) is a progressive neuronal disorder, leading to cognitive disorder and bradykinesia in patients. PD is characterized by aggregated a-synuclein and dopaminergic neurodegeneration, related with elevated ROS level and other biological pathways. As hitherto, a paucity of any potent medication against PD suggesting everlasting efficacy has stimulated advances in terms of research and quest for newer drugs. However, some novel therapies involving plant molecules are being exploited for adjunctive therapy and synthetic medicaments. Caenorhabditis elegans serves as a suitable in-vivo model with a healthier approximation of the real environment in the human body than in-vitro tests. In this venture, the present study was fabricated for the first time to decipher anti-Parkinson's effects of 2-Isopropyl-5-methylphenol (IPMP) employing C. elegans. IPMP is derived from Trachyspermum ammi, which contains anti-inflammatory and anti-apoptotic activity but no reports have yet described its effect on PD. Our study showed that IPMP significantly reduces a- synuclein aggregation within the worm's body. IPMP administration resulted in enhanced repulsive behavior towards chemorepellant, 1-nonanol indicating increased dopamine levels, which was further quantified by LC-MS/MS. Additionally, upon treatment with 6-OHDA, IPMP attenuates 6-OHDA-induced degeneration of DA neuron in worms. IPMP curtails ROS level and oxidative stress using H2-DCFDA and 5-Hydroxy-1,4-naphthoquinone, respectively. In the lead, staining with acridine orange, IPMP exhibited a significant decline in apoptosis. Altered lipid levels, another manifestation of PD were also found to normalize significantly in both wild type worms and NL5901 worms (Punc-54::a-synuclein::YFP+unc-119). Moreover, we furthered our studies towards deploying a qPCR technique for enumerating transcript expression of selected genes screened as a-synuclein modifiers from a genome-wide screen in C. elegans model of Parkinson's disease. In wild-type worms, we perceived a significant up-regulation of pink-1, ubc-12, spp-9, grk-2, lrk-1 and lagr-1 whereas pink-1, ubc-12, spp-9, grk-2 and pdr-1, mRNA expression levels were augmented in NL5901 worms. In concise, we conclude imminent areas of investigation, about the emerging nature of IPMP that can be exploited to provide mechanistic perceptions toward therapeutic intervention for PD. We hypothesize that the observed beneficial effect establishes the potential of IPMP as a possible candidate for ameliorative or supportive roles in the management of Parkinsonism.

Trivedi, S. et al. (2019) International Worm Meeting "Polymethoxyflavone 5-demethylnobiletin promotes DR induced autophagy dependent longevity in Caenorhabditis elegans."

Pandey, R., Trivedi, S.

[

International Worm Meeting,

2019]

Aging is a global concern that brings formidable socioeconomic and healthcare challenges. It is characterized as accumulation of deleterious changes in organelles, cells and tissues with expanding age that collectively responsible for the risk of several age associated diseases. In the last decade, various studies have shown evidences towards the utilization of plant derived molecules against aging and various neurological diseases. Here we report the identification of the polymethoxyflavone, 5-demethylnobiletin (DN) as a natural compound with anti-aging potential. We have utilized Caenorhabditis elegans as the model system to study anti-aging effects of DN in vivo (life span, lipofuscin accumulation, oxidative stress resistance, ROS levels lipid levels, pharyngeal pumping, reproductive span and total brood size) and pathway involved in underlying mechanism. DN is isolated from gum exudates of Gardenia lucida, which is known to possess rich anti-oxidant activity. We show that external administration of DN extends the lifespan and oxidative stress tolerance against artificial ROS inducer juglone, in a dose dependent manner. The studies revealed that lifespan extension is arbitrated through decreased levels of ROS (DCF-DA method), lipid levels (Nile red staining) and intestinal lipofuscin levels in both young adult and aged worms upon low dose administration of DN. Additionally, DN also reduces the pharyngeal pumping and enhances the reproductive span of worms. The interaction of DN with genes required for lifespan extension is deciphered by studying effect of DN on gene mutants and gene expression of these genes. DN activates dietary restriction (DR) pathway in nematodes mediated by pha-4, sir-2.1, skn-1 and eat-2 genes. We also show that DR induced lifespan requires the activation of autophagy genes viz. bec-1, unc-51 and lgg-1. This induction of both processes is fully required for lifespan extension in the worm. Moreover, mutant analysis is further validated by gene reporter assay (DA2123, LGG-1::GFP; SM481, PHA-4::GFP and LD1, SKN-1::GFP) and qPCR studies of relevant genes. Altogether, DN can enhance the lifespan of C. elegans via DR pathway which also requires the induction of autophagy mechanism.

load 10 more results