Browsing by Author "Rawal, Rakesh"

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    Attenuation of inorganic arsenic exposure-induced cognitive impairments by polyphenols-rich fraction of wild Rubus ellipticus berries via reshaping gut microbiota and reduction of oxidative stress-lead neuro-intestinal inflammation
    (Elsevier B.V., 2026) Vandana; Gupta, Shweta; Sharma, Rajni; Pandey, Ashutosh; Bishnoi, Mahendra; Rawal, Rakesh; Singh, Dhirendra Pratap; Das, Santasabuj
    The neurotoxic effects of inorganic arsenic exposure and consequential neurobehavioral outcomes involve activation of inflammatory cascades and reactive oxygen species (ROS)-mediated neuronal damage. Functional foods with characterized bioactive(s) are gaining attention in environmental contaminants-exposure induced pathologies. Here, we investigated the use of an ultrasonication-assisted extraction (UAE) and response surface methodology (RSM)-optimized process for polyphenols-rich extract from a Himalayan berry, Rubus ellipticus, against inorganic arsenic [iAs(III)]-induced cognitive impairments in mice. Total phenolic content (TPC), in-vitro antioxidant activity and cytotoxicities, along with UHPLC and LC-MS based polyphenolic profiles were determined. iAs(III)-exposure-induced spatial navigation tasks and passive avoidance-based learning performances were assessed. Neurochemical estimations, oxido-nitrosative stress markers, histological analysis and qRT-PCR-based gene expression in brain, ileum and, colon, pro-inflammatory cytokines and LPS levels, gut permeability, short chain fatty acids (SCFAs) levels, along with nanopore-based 16s rRNA metagenomics were performed. RSM-optimized UAE methods showed high TPC and antioxidant activities in polyphenol-rich (flavanols, phenolic acids and, proanthocyanidins) extract from R. ellipticus. The extract showed no potential cytotoxicity and significantly prevented iAs(III)-exposure-induced cognitive impairment, especially long-term spatial learning and memory. It also prevented altered neurotransmitter turnover, neuro-/ ileal/ colonic inflammation, and ROS-induced damages, increased ileum permeability, reduced SCFA level, and gut perturbations caused by iAs(III)-exposure. These findings suggest that the polyphenol-rich extract from Rubus ellipticus may offer protection against environmental toxicant [iAs(III)]-induced neurotoxicity and behavioral effects, potentially through combined modulation of oxidative stress, neuroinflammation, and gut-related pathways.
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    Polyphenols-rich Indian barberry berries extract alleviates inorganic arsenic exposure-induced cognitive impairments and associated gut microflora alterations
    (Elsevier B.V., 2026) Vandana; Gupta, Shweta; Sharma, Rajni; Pandey, Ashutosh; Bishnoi, Mahendra; Rawal, Rakesh; Das, Santasabuj; Singh, Dhirendra Pratap
    Arsenic, a globally prevalent environmental toxin that can lead to neuro-behavioural changes. Oxidative stress and activation of inflammatory cascades are prominent mechanisms underlying these effects. The present study investigated the effects of polyphenol-rich extracts from Berberis aristata (Indian barberry) against inorganic arsenic-induced cognitive impairments in a murine model and presented mechanistic insights into its functional food properties. Response Surface Methodology (RSM)-guided hydro-alcoholic extracts were prepared and chemically characterized for their antioxidant activity, total phenolic contents (TPC) and free radical scavenging activities (RSA). UHPLC and LC-MS-based profiling of polyphenols, anthocyanins, and proanthocyanidins was performed. In-vitro toxicity studies in hepatic and colonic cancer cell lines, followed by in-vivo evaluation of these extracts in inorganic arsenic-exposed mice for spatial navigation tasks and passive avoidance-based learning were performed. Further assessments included neurotransmitter levels, histopathological investigations, qRT-PCR-based gene expression analysis, inflammatory cytokines and oxido-nitrosative stress markers in the brain and gastrointestinal tract, Evan's blue dye-based ileum permeability, and short chain fatty acids (SCFAs) estimation, along with Oxford Nanopore-based 16S rRNA metagenomics in cecal contents and PICRUSt2-based functional prediction of metagenomic data. RSM-optimized methods for polyphenol extraction yielded extracts with high TPC and RSA, with flavanols, phenolic acids, and proanthocyanidins identified as major polyphenols, and no in-vitro toxicity was observed. The extracts significantly prevented arsenic exposure-induced cognitive impairment, altered neurotransmitter turnover, neuroinflammation and gastrointestinal tract inflammation, oxidative stress-induced damage, increased ileum permeability, SCFA alteration, and gut microbial dysbiosis. These findings underscore the therapeutic/preventive potential of this polyphenol-rich extract against environmental toxicant-induced neurotoxicity, potentially involving gut microbiota-associated pathways.