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Parkinsonism is an age-associated neurodegenerative disorder characterized by aggregation of α-synuclein (α-syn) protein in the substantia nigra region, degeneration of dopaminergic neurons, and deregulated lipid metabolism. Currently, only symptomatic relief has been provided by FDA-approved therapeutic approaches for Parkinson's disease (PD). The present study aims to evaluate the potential of wedelolactone (WDL), a natural occurring coumestan found in Eclipta alba to mitigate the parkinsonism in Caenorhabditis elegans disease model. In the present studies, supplementation with 37.5 μM WDL exhibited a reduction in the level of α-syn in an age-dependent manner (22% at day 5, p < 0.05; and 16% at day 10, p < 0.001, n = 30), along with improvement in neuronal health through basal movement, and elevated the dopamine levels evident through 1-nonanol repulsion results in wild-type and diseased worms. Moreover, WDL augmented the mitochondrial health in wild-type, PD-diseased, and mev-1 mutant worms that establish the inherent activity of WDL in the alleviation of oxidative stress. Furthermore, WDL supplementation significantly decreases the neutral lipid and triglyceride level and also alleviates protein carbonyl level in PD disease condition. The overall investigation will provide a pioneer to the future insights of PD research related to plant-based drugs. qPCR studies after WDL supplementation revealed alteration of genes involved in the regulation of various stress-responsive (sod-5, gst-4, skn-1), α-syn-suppressing (lrk-1, ymel-1, lagr-1, grk-1), and mitochondrial (pink-1) genes. All together, these findings support that the WDL is a promising candidate to combat age-related multi-factorial PD pathology associated with protein misfolding and accumulation. The results provide sufficient information in the development of therapeutic medicines from natural products for improving the health.

The study elucidates the effect of ɑ-linolenic acid (ALA) on mitochondrial stress, hypoxic cancer microenvironment, and intervention of cholinergic anti-inflammatory pathway using N-methyl-N-nitrosourea (MNU) induced estrogen receptor (ER+) mammary gland carcinoma and Caenorhabditis elegans model, respectively. The efficacy of ALA was scrutinized in vivo and in vitro using various experiments like hemodynamic studies, morphological analysis, antioxidants parameters, immunoblotting, and quantitative reverse transcription polymerase chain reaction. The effect of ALA was also validated using C. elegans worms. ALA administration had a positive effect on tissue architecture of the malignancy when scrutinized through the whole mount carmine staining, hematoxylin and eosin staining, and scanning electron microscopy. The proteomic and genomic checkpoint revealed the participation of mitochondrial dysfunction, alteration of hypoxic microenvironment, and involvement of cholinergic anti-inflammatory response after treatment with ALA. ALA treatment has also increased the level of synaptic acetylcholine and acetylcholine esterase with a significant decrease in lipid content. It was concluded that ALA persuaded the mitochondrial stress, activation of downstream cholinergic anti-inflammatory markers, and favorable regulation of hypoxia microenvironment through inhibition of fatty acid synthase and sterol regulatory element-binding protein., (© 2018 Wiley Periodicals, Inc.)

Microbial interference plays an imperative role in plant development and response to various stresses. However, its involvement in mitigation of oxidative stress generated by plant parasitic nematode in plants remains elusive. In the present investigation, the efficacy of microbe's viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 single and in combinations was examined to mitigate oxidative stress generated by M. incognita in medicinal plant, Bacopa monnieri. Microbial combination with and without pathogen also enhanced the growth parameters along with secondary metabolites (bacoside) of B. monnieri than the pathogen inoculated control. The study showed that initially the production of hydrogen peroxide (H 2 O 2 ) was higher in dual microbes infected with pathogen which further declined over M. incognita inoculated control plants. Superoxide dismutase and free radical scavenging activity were also highest in the same treatment which was linearly related with least lipid peroxidation and root gall formation in B. monnieri under the biotic stress. Microscopic visualization of total reactive oxygen species (ROS), H 2 O 2 , superoxide radical and programmed cell death in host plant further extended our knowledge and corroborated well with the above findings. Furthermore, scanning electron microscopy confirmed good microbial colonization on the host root surface around nematode penetration sites in plants treated with dual microbes under pathogenic stress. The findings offer novel insight into the mechanism adopted by the synergistic microbial strains in mitigating oxidative stress and simultaneously stimulating bacoside production under pathogenic stress., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system. The effect on aging is evaluated by studying effect of PHE on mean survival in worms. The stress modulatory potential was assessed by quantification of intracellular ROS level, autofluorescent age pigment lipofuscin, oxidative and thermal stress assays. Additionally, stress response was quantified using gene reporter assays. The 0.01 µg/ml dose of PHE was able to enhance mean lifespan by 16.09% (P < 0.0001) in C. elegans. Furthermore, PHE treated worms demonstrated oxidative stress resistance in both wild type and stress hypersensitive mev-1 mutant along with upregulation of stress response genes sod-3 and gst-4. The delayed aging under stress can be attributed to its direct reactive oxygen species-scavenging activity and regulation of some age associated genes like daf-2, daf-16, skn-1, sod-3 and gst-4 in wild-type worms. Additonally, PHE delayed age related paralysis phenotype in CL4176 transgenic worms. Altogether, our results suggest PHE significantly improves the oxidative stress and life span in C. elegans. Overall the present study suggests this polyherbal formulation might play important role in regultaing aging and related complications like diabetes.

The progression in lifespan has been associated with elevated intracellular reactive oxygen species (ROS) and oxidative stress level which contributes to development of age related disorders. The discovery of lifespan modulating phytomolecules may promote development of natural therapies against age related afflictions. Acacetin (5,7-dihydroxy-4-methoxyflavone), is a naturally occurring flavonoid known to possess therapeutic properties. To this end, the present study evaluates effect of acacetin (AC) on lifespan, stress and neurotoxicity for the first time by using well-established free living, multicellular Caenorhabditis elegans model system. The 25 μM dose of AC significantly prolonged the mean lifespan of worms by 27.31% in comparison to untreated control and other tested doses of AC. Additionally, AC enhanced stress resistance against oxidative and thermal stress in worms. Furthermore, AC attenuated age related intracellular ROS level, aggregation of age pigment lipofuscin and increased the mean survival in stress hypersensitive mev-1 mutant by 40.5%. AC supplementation also reduced the alpha synuclein aggregation in transgenic worm model of Parkinson's disease. The enhanced stress resistance, lifespan and alleviation of age related pathology can be attributed to increment in stress modulatory enzymes like superoxide dismutase (SOD) and catalase (CAT) level. Altogether the results suggest AC exposure maintains stress level, health span and extends mean lifespan of C. elegans. The longevity promoting and neuromodulatory effects of AC are mediated by up regulation of the stress response genes sod-3 and gst-4. The present finding gives new insights of natural remedies and their future prospects in developing therapeutic interventions for managing age related diseases.

Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments., Competing Interests: The authors declare that they have no competing interests.

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.

Drought is a major limiting factor for rice (Oryza sativa L.) production globally, and a cost-effective seed priming technique using bio-elicitors has been found to have stress mitigating effects. Till date, mostly phytohormones have been preferred as bio-elicitors, but the present study is a novel attempt to demonstrate the favorable role of micronutrients-phytohormone cocktail, i.e., iron (Fe), zinc (Zn), and methyl jasmonate (MJ) via seed priming method in mitigating the deleterious impacts of drought stress through physio-biochemical and molecular manifestations. The effect of cocktail/priming was studied on the relative water content, chlorophyll a/b and carotenoid contents, proline content, abscisic acid (ABA) content, and on the activities of ascorbate peroxidase (APX), superoxide dismutase (SOD), NADPH oxidase (Nox), and catalase (CAT). The expressions of drought-responsive genes OsZn-SOD, OsFe-SOD, and Nox1 were found to be modulated under drought stress in contrasting rice genotypes -N-22 (Nagina-22, drought-tolerant) and PS-5 (Pusa Sugandh-5, drought-sensitive). A progressive rise in carotenoids (10–19%), ABA (18–50%), proline (60–80%), activities of SOD (27–62%), APX (46–61%), CAT (50–80%), Nox (16–30%), and upregulated (0.9–1.6-fold) expressions of OsZn-SOD, OsFe-SOD, and Nox1 genes were found in the primed plants under drought condition. This cocktail would serve as a potential supplement in modern agricultural practices utilizing seed priming technique to mitigate drought stress-induced oxidative burst in food crops. [ABSTRACT FROM AUTHOR]

5′-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone (5-HPF), a polymethoxyflavone compound found in dikamali gum, has been shown to exert a range of beneficial effects on health. We have previously reported that 5-HPF improves the cholinergic dysfunction and also possesses antioxidant properties in Caenorhabditis elegans. In this study, we have identified the effect of 5-HPF on the worm lifespan and its underlying molecular mechanisms. Out of the five tested pharmacological doses of 5-HPF, viz. 6.25, 12.5, 25, 50, and 100 μM, the 50 μM dose maximally extended the mean life of C. elegans by 28%. The present study revealed that 5-HPF supplementation leads to dietary restriction (DR)-like effects in the worms without altering bacterial metabolism. The analysis of mutant animals fed with 5-HPF suggested that the extended lifespan of C. elegans depends upon multiple DR-related signaling pathways, with NRF2 and FOXA being critical factors. Further investigation into the mechanistic aspects indicated that 5-HPF utilizes autophagy pathway induced by DR through the upregulation of autophagy genes bec-1 and lgg-1, evident from the increase in autophagic puncta in the seam cells of lgg-1::gfp tagged worms. This study identifies the longevity-promoting activity of 5-HPF in C. elegans regulated by oxidative stress-resistance genes and DR-induced autophagy pathway. [ABSTRACT FROM AUTHOR]

Abstract 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 (25 μM) 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 (25 μM) 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. Highlights • BOB promote longevity in Caenorhabditis elegans. • BOB enhances stress resistance (Oxidative, Thermal etc.) and reduces lipofuscin in C. elegans. • BOB recover the shortened lifespan of oxidative stress prone mutants mev-1 and gas-1. • BOB enhanced the expressions of SOD-3, GST-4 and HSP-16.2 transgenic strains of C. elegans. • The BOB deserves future investigations for treating age related disorders. [ABSTRACT FROM AUTHOR]

Background: The various herbal remedies have been used in Ayurveda which symbolizes traditional medicine system since ancient times. The increasing popularity of herbal medicines has prompted us toward the development of natural therapeutics for preventing neurodegenerative disease such as Alzheimer's disease (AD) in living organisms. This study focused on a flavonoid compound 5,7-dihydroxy-4-methoxyflavone (DMF) also known as acacetin which is a major constituent of Premna odorata (L.) plant. This bioactive flavonoid exhibits several medicinal properties such as antimicrobial, anti-inflammatory, antioxidant, and anti-carcinogenic. Objective: The aim is to determine the protective effects of DMF against amyloid beta (Aβ)-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans model of AD. Materials and Methods: The therapeutic potential of DMF treatments (5, 25, and 50 μM) was investigated to counteract Aβ paralysis and oxidative stress through paralysis assay, reactive oxygen species (ROS) detection, protein carbonylation, aldicarb assay, and mRNA quantification using transgenic C. elegans model of AD. Results: The present study reports that DMF effectively delayed Aβ-induced paralysis, attenuated ROS level reduced protein carbonylation and conferred aldicarb resistance. In addition, DMF was also found to up-regulate the expression of stress modulating (sod-1, sod-2, sod-3, ctl-1, hsp-16.2, and gst-4), acetylcholine transporter(unc-17), regulator of nicotinic acetylcholine receptor (unc-50), and choline acetyltransferase (cha-1) related genes. Conclusion: These findings suggest DMF may provide protection against Aβ toxicity and oxidative stress due to its antioxidant activity. Therefore, the bioactive flavonoid DMF may provide invaluable medicinal and health benefits which can delay the onset of age-related diseases. [ABSTRACT FROM AUTHOR]

Aging is an unavoidable phenomenon, often afflicting structure and functionality of body, marked with onset of age associated manifestations. Parkinson's disease (PD), the second most common form of dementia is manifested with Lewy body formation and dopaminergic dysfunction. Present study explores silymarin, a known hepatoprotective regimen for its efficacy in Aging and PD using Caenorhabditis elegans . Silymarin positively modulated longevity, reduced oxidative stress, independent of feeding behaviour. Up-regulation of longevity and stress related genes daf-16, sod-3, gst-4 and skn-1 indicate the possible involvement of these genes for regulating longevity. In-addition silymarin alleviated PD symptoms by reducing α-synuclein levels, lipid accumulation and enhanced dopamine function. Silymarin executes its beneficial effects through mitigation of free radicals, while achieving alleviation in Parkinsonism possibly through pdr-1 mediated recruitment of ubiquitin proteasome system as evident from qPCR studies. Altogether, silymarin emerged as a potent molecule for investigation in Aging and age related disorders. [ABSTRACT FROM AUTHOR]

The advancements in the field of gerontology have unraveled the signaling pathways that regulate life span, suggesting that it might be feasible to modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) from Premna integrifolia and evaluated its antiaging effects in Caenorhabditis elegans The spectral data analysis revealed the occurrence of a new compound ARX. Out of the three tested pharmacological doses of ARX, viz. 5, 25, and 50 µM, the 25-µM dose was able to extend life span in C. elegans by more than 39%. The present study suggests that ARX affects bacterial metabolism, which in turn leads to dietary restriction (DR)-like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat-2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span extension involves mechanisms associated with DR and maintenance of cellular redox homeostasis. This study is the first time report on longevity-promoting activity of ARX in C. elegans mediated by stress and DR-regulating genes. This novel phytomolecule can contribute in designing therapeutics for managing aging and age-related diseases. [ABSTRACT FROM AUTHOR]

In traditional systems of medicine, plants belonging to the family Rutaceae have been used against ageing and associated debilitating changes. Considering the therapeutic potential of limonene (C10H16), the principal component of the Rutaceae family plants, the present study was designed to decipher lifespan and stress-modulating potential of monocyclic terpene limonene (LM) employing genetically tractable model system Caenorhabditis elegans. Furthermore, we tested oxidative stress tolerance and in vivo reactive oxygen species build-up, which was monitored with or without exposure to LM. Additionally, involvement of transcription factor DAF-16 was examined in terms of nuclear localization. Overall, this study has implications for developing future anti-ageing pharmacological strategies in the future. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L) is a staple food crop for more than half of the world population, however its yield is adversely affected by drought stress. Traditional rice varieties have significant variability in morphological, physiological and molecular adaptation to drought stress but modern high-yielding cultivars are quite sensitive to drought. Here, we screened a set of 2000 EMS-mutants of a drought tolerant 'Aus' rice cultivar 'Nagina 22′ (N22) using standard evaluation system of drought sensitivity (DRS) score and identified 73 mutants with either higher or lower DRS score than wild type (WT) N22. The mutants were also screened for epicuticular wax (EW) content to identify 25 mutants with altered levels of EW content, all of which were common to the DRS mutants. The remaining DRS mutants with EW content similar to WT N22 must have other mechanisms of drought tolerance. The identified mutants were evaluated for drought related physiological traits, drought sensitivity index (DSI) and agronomic performance for four consecutive years to understand the role of EW in drought tolerance. All the EW mutants showed altered levels of DSI, biomass and grain yield. The mutants also showed changes in chlorophyll content, relative water content, cell membrane stability and oxidative stress enzyme activities. The high-EW mutants showed lower DRS scores but higher RWC, biomass and grain yield under drought than WT N22, while low-EW mutants showed the opposite trends. The gain and loss of drought tolerance mutants identified here would help gain further insights into the mechanism of drought tolerance and gene discovery for the trait in N22. A high-EW low-DSI mutant viz., 'M59′ with substantially higher grain yield under drought will serve as useful donor for breeding drought tolerant rice cultivars for rainfed upland agroecological regions. • EMS-mutants of rice with loss or gain of drought tolerance trait were identified. • Multi-year evaluation of mutants for physiological and agronomic traits under drought was done. • Epicuticular wax content was directly correlated with drought tolerance in rice. • High-wax mutants of rice with low yield losses under drought were identified. • Drought tolerant mutants of rice with mechanism other than epicuticular wax were identified. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) and β-caryophellene (BCP) are well known bioactive phytomolecules which are known to reduce oxidative stress in living organisms. Therefore, the present study was envisaged to explore the possible effects of CUR and BCP in suppression of cadmium quantum dots (CdTe QDs) induced toxicity in Caenorhabditis elegans. CdTe QD are luminescent nanoparticles extensively exploited for in vivo imaging, but long term bioaccumulation confer deleterious effects on living organisms. The 24-h LC 50 and LC 100 of CdTe QD were found to be 18.40 μg/ml and 100 μg/ml respectively. The CdTe QD exposure elevated HSP-16.2 expression mediating induction of the stress response. The CdTe QD lethality was due to increment in ROS and decline in SOD and GST expression. The present study demonstrates improved survival in BCP (50 μM) and CUR (20 μM) treated worms by over 60% ( P < 0.01) and 50% ( P < 0.029) in CdTe QD (100 μg/ml) exposed worms. Furthermore, BCP and CUR attenuate oxidative stress triggered by QD. The present study for the first time demonstrates CdTe QD toxicity remediation via BCP and CUR. The future investigations can unravel underlying protective effects of phytomolceules for remediating cyotoxicolgical effects of QDs. [ABSTRACT FROM AUTHOR]

Specioside (6-O-coumaroylcatalpol) is an iridoid glucoside which possesses multifunctional activities viz. analgesic, antidyspeptic, astringent, liver stimulating and wound healing properties. The present study for the first time delineates stress alleviating and lifespan prolonging action of specioside (SPC), isolated from Stereospermum suaveolens in the free living, multicellular nematode model Caenorhabditis elegans . A strong correlation between lifespan extension and stress modulation in adult worms was established in a dose dependent manner. The dietary intake of this phytomolecule elevated juglone induced oxidative and heat induced thermal stress tolerance in C. elegans . On evaluation, it was found that 25 μM dose of SPC significantly extended lifespan by 15.47% ( P ≤ 0.0001) with reduction in stress level. Furthermore, SPC enhanced mean survival in mev-1 mutant suggesting its oxidative stress reducing potential. Furthermore, SPC augmented stress modulatory enzymes superoxide dismutase (SOD) and catalase (CAT) level in C. elegans . Altogether, these findings broaden current perspectives concerning stress alleviating potentials of SPC and have implications in development of therapeutics for curing age related disorders. [ABSTRACT FROM AUTHOR]