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Abstract Ageing is a progressive deterioration in functional and structural well-being of the body, accompanied with age-associated neurological disorders such as Parkinson's disease (PD), Alzheimer's disease and Huntington's disease. PD is marked with motor function decline, progressive neurodegeneration due to aggregation of insoluble α-synuclein in the dopaminergic neuron. Here we investigated the effect of tambulin (3,5-dihydroxy-7,8-dimethoxy-2-(4-methoxyphenyl) chromen-4-one), a hydroxy substituted flavanol isolated from fruits of Zanthoxyllum armatum DC (Family-Rutaceae) for its longevity promoting and neuromodulatory activities using Caenorhabditis elegans model system. Our results show that tambulin treatment significantly enhance lifespan and stress tolerance in worms, along with mitigation of ageing biomarkers like lipofuscin and protein carbonyl. In line with the alleviated ROS levels, tambulin treatment led to upregulated mRNA expression of ROS scavenging genes viz., sod-1 , sod-3 , and ctl-2. Upregulation in daf-16 gene indicates the involvement of insulin signaling pathway in tambulin mediated longevity. Tambulin treatment exhibited curtailed PD manifestations in terms of reduced α-synuclein levels, lipid accumulation, improved locomotary behavior and dopamine levels. Altogether, our data suggest that tambulin mediated alleviation of PD manifestations possibly involved PD counter protective machinery as evident through upregulated mRNA expression of lagr-1 , ymel-1 , pdr-1 , ubc-12 , and lrk-1. Our studies present tambulin as a potential molecule for its properties against ageing and Parkinson's disease. Further studies are speculated to realize the mechanistic and pharmacological aspects of tambulin. Highlights • Tambulin enhances stress tolerance through modulation of ROS scavenging genes viz., sod-1 , sod-3 , and ctl-2. • Tambulin induced longevity shows the involvement of daf-16 mediated insulin signaling pathway. • Tambulin activates PD protective lagr-1 , ymel-1 , pdr-1 , ubc-12 , and lrk-1 genes. [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]

Distillery wastewater has significant amount of coloring compounds and organic substances even after the secondary treatment process, which poses many severe environmental and health threats. However, the recalcitrant coloured compounds have not yet been clearly identified. In this study, two bacterial strains DS3 and DS5 capable to decolorize distillery wastewater (DWW) pollutants were isolated and characterized as Staphylococcus saprophyticus (MF182113) and Alcaligenaceae sp. (MF182114), respectively. Results showed that mixed bacterial culture was found more effective decolorizing 71.83% DWW compared to axenic culture DS3 and DS5 resulting only 47.94% and 50.67% decolorization, respectively. The FT-IR and LC-MS/MS analysis of untreated DWW showed the presence of many recalcitrant compounds having different functional groups, but after bacterial treatment, most of compounds get diminished and the toxicity of DWW was reduced significantly. Further, the Nile red staining of Caenorhabditis elegans exposed to untreated and bacteria treated DWW for evaluation of toxicity assay and results revealed that the worms exposed to untreated DWW showed sharp reduction in total fat content having more profound effects, suggesting the diminished nAchR signaling as compare to bacterial treated DWW. Hence, this study revealed that inadequate disposal of untreated DWW may cause transfer of toxic substances into the environment and receiving water bodies. Image 1 • Distillery wastewater has a variety of chemical pollutants. • Bacteria Staphylococcus saprophyticus and Alcaligenaceae sp. were used to treat DWW. • FT-IR and LC-MS used to characterize the DWW pollutants and their metabolites. • Toxicity of DWW pollutants and metabolites was evaluated by Caenorhabditis elegans. • Study showed disposal of untreated DWW may cause severe environmental pollution. [ABSTRACT FROM AUTHOR]

Cholinergic function is compromised in plethora of neurodegenerative disorders especially Alzheimer’s disease. Increasing acetylcholine (ACh) levels has been the mainstay in majority of the therapeutic regimens, accepted for management of disease. The present study investigates the efficacy of 5-Desmethylnobiletin (DN), a polymethoxyflavone in augmenting cholinergic function using Caenorhabditis elegans as a model organism. The studies revealed significant elevation in cholinergic transmission mediated through increased levels of ACh and activity of nicotinic acetylcholine receptors (nAChR). Further investigation into the mechanistic aspects indicated that DN enhanced cholinergic function through down modulation of acetylcholinesterase activity at enzyme and transcript level along with upregulation of non alpha subunit, unc-29 which could be linked with enhanced nAChR activity as evident from levamisole assay. Additionally, studies on antioxidant properties, implicated significant potential of DN in curtailing ROS, both in vivo and in vitro. Our studies present DN as a phytomolecule with novel biological activities which could be exploited and researched upon for therapeutic avenues in terms of cholinergic function and antioxidant potential. [ABSTRACT FROM AUTHOR]

The ailments related to a malfunction in cholinergic functioning currently employ the use of inhibitors for acetylcholinesterase (AChE) and N -methyl- d -aspartate (NMDA) receptors. The present study was designed to elucidate the potential of swertiamarin (SW), a secoiridoidal glycoside isolated from Enicostemma littorale in curtailing the cholinergic dysfunction. Using Caenorhabditis elegans as a model, SW was found to enhance neurotransmission by modulating AChE and nicotinic acetylcholine receptor (nAChR) activity; being orchestrated through up-regulation of unc-17 and unc-50. SW exhibited AChE inhibition both in vivo and cell-free system. The in silico molecular docking of SW and human AChE (hAChE) displayed good binding energy of −6.02. Interestingly, the increase in aldicarb and levamisole sensitivity post SW treatment was curtailed to a significant level in daf-16 and skn-1 mutants. SW raised the level of the endogenous antioxidant enzymes through up-regulation of sod-3 and gst-4 that act downstream to DAF-16 and SKN-1, imparting protection against neurodegeneration. The outcome of our study displays SW as a potential natural molecule for the amelioration of cholinergic dysfunction. Moreover, the study also indicates that SW elicits antioxidant response via up-modulation of daf-16 possibly through unc-17 upregulation. Further research on SW pertaining to the underlying mechanism and potential is expected to significantly advance the current understanding and design of possible ameliorative or near ameliorative regimens for cholinergic dysfunction. • Swertiamarin, a secoiridoid glycoside elevates the cholinergic neurotransmission by modulating synaptic AChE and nicotinic acetylcholine receptor activity (nAChR) in Caenorhabditis elegans. • Swertiamarin activates unc - 17 and unc - 50 genes which are related to acetylcholine vesicular transport and receptor respectively. • Swertiamarin also provide neuroprotection through modulation of ROS scavenging genes viz. sod-1 , sod-3 , and gst-4. • SW elicits antioxidant response via up-modulation of daf-16 possibly through unc-17 upregulation. [ABSTRACT FROM AUTHOR]