Understanding the impact of Plant-Derived Food Grade Substances PDFGS on metal-induced neurodegeneration: A systematic review of preclinical evidence

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BackgroundThe cascade of events involved in metal-induced neurotoxicity is described as complex and are linked to the chemical properties of the metals involved. These events include alterations of membrane properties, impairment of neurotransmission, oxidative stress, inflammation, deregulation of cell signaling, and apoptosis. Yet the mechanisms of metal induced neurotoxicity is not clear. However, in recent times studies have shown that natural dietary and plant products may contain potent constituents that may be used to treat diverse neurological disorders. ObjectiveThe aim of this systematic review was to summarize recent literature on mechanisms of selected PDFGS in attenuating metal-induced neurotoxicity and neurodegeneration. MethodologyLiterature search was carried out in scientific databases such as PubMed, Scopus, Web of Science, Google Scholar, Environmental Index, Toxline, and Toxnet. A modified variant of the CONSORT checklist was used to assess the quality of in vitro studies while the SYRCLE assessment tool was used for the assessment of the risk of bias for in vivo studies. A total of 20 studies were included in the systematic review (in vitro studies (6) and animal studies (14)). ResultsEvidence collated in this review highlighted mechanisms involved in the activities of PDFGS which include; attenuation of metal-induced alterations of neurotransmission impairment (curcumin, hesperidin, berberine), synaptic dysfunction (curcumin, hesperidin, berberine), mitochondrial dysfunction (curcumin, hyperforin), oxidative stress(curcumin, Mangiferin, tannic acid, hesperidin, genistein, gastrodin, quercetin, dihydromyricetin), neuroinflammation(mangiferin, fisetin, curcumin, hesperidin, gastrodin, quercetin), dysregulation of cell signaling(curcumin, hesperidin, berberine, and apoptosis(fisetin, mangiferin, curcumin, berberine, tannic acid, hesperidin, genistein, gastrodin, quercetin, dihydromyricetin). ConclusionIn all, in-depth mechanistic insights of metal-induced neurotoxicity, as well as the knowledge of PDFGS neuroprotective mechanisms will make significant progress in the development of therapeutic interventions for the prevention and alleviation of metal-induced neurotoxicity and neurodegeneration.