Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation

Cheah, Irwin K.; Tang, Richard Ming Yi; Yew, Terry S. Z.; Lim, Keith H.C.; Halliwell, Barry

doi:10.1089/ars.2016.6778

Cited by 126 publications

(157 citation statements)

References 65 publications

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“…This extension in mean and maximal lifespan with ET treatment would equate to years when translated to a human lifespan, but more importantly, the increased healthspan would lead to a significant reduction in morbidity and societal burden. It should also be noted that numerous animal and human studies have demonstrated that blood and tissue levels of ET are capable of reaching millimolar levels hence validating the feasibility of the doses tested in the nematodes .…”

Section: Discussionmentioning

confidence: 84%

Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

Cheah

et al. 2019

FEBS Letters

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The abnormal accumulation of β‐amyloid peptide (Aβ) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aβ‐mediated neurotoxicity remain elusive, Aβ has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione‐derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET’s potential to counteract Aβ‐toxicity in transgenic Caenorhabditis elegans overexpressing a human Aβ peptide. The accumulation of Aβ in this model leads to paralysis and premature death. We show that ET dose‐dependently reduces Aβ‐oligomerization and extends the lifespan and healthspan of the nematodes.

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Section: Discussionmentioning

confidence: 84%

Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

Cheah

et al. 2019

FEBS Letters

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“…Ergothioneine can accumulate to high levels in some human and animal tissues, including red blood cells (with basal levels of ~ 125 μ m and ~ 220 μ m in human and mouse whole blood, respectively, and millimolar levels reported in red blood cells ), liver and spleen (with basal levels of ~ 350 μmol·g −1 tissue and ~ 100 μmol·g −1 tissue in mouse liver and spleen, respectively) . Our recent study demonstrated that when ET is orally administered to mice, it accumulates rapidly in the liver and blood cells but also enters most (or perhaps all) other tissues, including brain, heart, lung, kidney, spleen and eye.…”

Section: Ergothioneine In Tissues Extracellular Fluids and Cell Culturementioning

confidence: 97%

“…Dietary ET in animals (including humans) is absorbed by means of an intestinal transporter, OCTN1, that has a high degree of specificity . The same transporter then distributes ET to most or all body tissues: excretion from the body is slow and administered ET is highly retained in human and other animal body tissues and red blood cells . This implies that ET has a useful function, otherwise why absorb and retain it?…”

Section: Ergothioneine a Natural “Antioxidant”?mentioning

confidence: 99%

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Ergothioneine – a diet‐derived antioxidant with therapeutic potential

2018

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Ergothioneine is a thiol/thione molecule synthesised only by some fungi and bacteria. Nonetheless, it is avidly taken up from the diet by humans and other animals through a transporter, OCTN1, and accumulates to high levels in certain tissues. Ergothioneine is not rapidly metabolised, or excreted in urine and is present in many, if not all, human tissues and body fluids. Ergothioneine has powerful antioxidant and cytoprotective properties in vitro and there is evidence that the body may concentrate it at sites of tissue injury by raising OCTN1 levels. Decreased blood and/or plasma levels of ergothioneine have been observed in some diseases, suggesting that a deficiency could be relevant to the disease onset or progression. This brief Review explores the possible roles of ergothioneine in human health and disease.

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“…Although not our subject here, the biology of ergothioneine (an antioxidant) is very interesting (see e.g. [126,199,[210][211][212]), with SLC22A4 -/-cells being very sensitive to oxidative stress, but the key point is that this analysis shows the likelihood that many transporters were actually selected on the basis of their ability to take up dietary, bioactive compounds that are effectively xenobiotics [213]. Cloning large libraries of chromosome fragments [94,214], and seeing their effects on export or productivity, or assessing genes with increased transcription in response to increased external metabolite concentrations [108,215] provide for other methods (see e.g.…”

Section: Figure 3 An Untargeted Metabolomics Strategy For Determininmentioning

confidence: 99%

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Kell¹

2018

Preprint

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The yield and ease of purification of biotechnological products are typically greatly enhanced if they can be secreted into the external medium. Although not universally appreciated, however, small molecule biotechnological products do not ‘float across’ the phospholipid bilayer portion of biological membranes, and thus they need transporters to assist their passage into the extramembrane and extracellular spaces. Some of these transporters may be reversible, equilibrative transporters that might more normally be used for uptake, while others may have an efflux directionality imposed on them via suitable energy coupling mechanisms. Despite the energetic costs of small molecule synthesis, natural evolution does in fact provide a number of mechanisms by which the secretion of such products can actually enhance fitness. Where available these provide useful starting points, and assaying for such activities is crucial. In particular, in a systems biology approach, we first need to identify such/suitable activities before we can seek to increase them. They may then be improved through promoter engineering, via manipulation of control elements, or by directed evolution of the transporter proteins themselves. Modern methods of synthetic biology provide enormous opportunities for all kinds of efflux transporter engineering; they are just beginning to be realised.

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Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation

Cited by 126 publications

References 65 publications

Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

Ergothioneine – a diet‐derived antioxidant with therapeutic potential

Control of metabolite efflux in microbial cell factories: current advances and future prospects

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