Ergothioneine, recent developments

Cheah, Irwin K.; Halliwell, Barry

doi:10.1016/j.redox.2021.101868

Cited by 111 publications

(104 citation statements)

References 162 publications

(268 reference statements)

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“…Dysregulation of GSH synthesis contributes to the pathogenesis of liver diseases 15 . Moreover, ergothioneine, a ubiquitous sulfur-containing compound (100–2 mmol/L) in animals, is synthesized only by a few microorganisms and acts as an antioxidant and cytoprotectant 16 , 17 . Furthermore, taurine is an abundant amino sulfonic acid with diverse cytoprotective activities, including antioxidant activity 18 .…”

Section: Introductionmentioning

confidence: 99%

Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

Kurosawa¹,

Sugimoto²,

Imai

et al. 2021

Sci Rep

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Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.

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Section: Introductionmentioning

confidence: 99%

Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

Kurosawa¹,

Sugimoto²,

Imai

et al. 2021

Sci Rep

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“…A significant body of preclinical data has demonstrated antioxidant and anti-inflammatory activities of ergothioneine that are relevant to the prevention of cardiometabolic diseases [4,5]. These data underpinned our decision to first investigate ergothioneine in people with metabolic syndrome, who are at risk of developing diabetes and non-alcoholic fatty liver disease (NAFLD), as well as cardiovascular and atherothrombotic diseases [21].…”

Section: Discussionmentioning

confidence: 99%

“…An amino acid betaine (2-mercapto-histidine trimethylbetaine), ergothioneine has robust cytoprotective properties with roles as a metal chelator as well as an antioxidant, scavenging hydroxyls and other free radicals [3]. As recently reviewed in detail, a growing body of evidence implicates ergothioneine as an important nutrient for healthy ageing and the prevention of a variety of inflammatory diseases, including cardiometabolic diseases [4,5]. Notably, a long-term prospective cohort study (n = 3236 participants with median follow-up of 21.4 years) found that higher plasma levels of ergothioneine were associated with significantly lower risk of coronary disease, cardiovascular mortality and overall mortality (hazard ratios per 1 SD increment of ergothioneine 0.85, 0.79 and 0.86 respectively), as well as a more 'health-conscious food pattern' [6].…”

Section: Background and Rationalementioning

confidence: 99%

“…Although many SLC22 family members are non-selective transporters, evidence suggests that SLC22A4 is highly specific for ergothioneine [9,10]. Widely expressed in most tissues, SLC22A4 is particularly highly expressed in the small intestine where it functions to take ergothioneine up from the diet, and in the kidney where it is presumed to function in renal reabsorption [5]. A pharmacokinetic study of healthy humans taking encapsulated ergothioneine (5 and 25 mg/day) found that ergothioneine is rapidly absorbed and largely retained by the body, with large increases in plasma ergothioneine levels and only minimal increases (< 4%) in urinary excretion observed [11].…”

Section: Background and Rationalementioning

confidence: 99%

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Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study

Tian

Cioccoloni

Naseem

et al. 2021

Pilot Feasibility Stud

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Background Ergothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome. Methods We have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables. Discussion The ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial. Trial registration ISRCTN, ISRCTN25890011 Registered February 10th, 2021

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“…It had been found to catalyse the uptake of carnitine, and also that of the the non-physiological tetraethylammonium cation. However, the rates were in fact quite miserable, and it was not until Gründemann and colleagues used what was effectively an untargeted metabolomics approach [ 103 ] that it was discovered that it was in fact “really” a concentrative, sodium-coupled transporter for the nutraceutical ergothioneine [ 251 , 252 ] and also for the related stachydrine (proline betaine) [ 103 , 253 , 254 ]. Equivalently, this example also serves to illustrate how finding a transporter with one activity does not mean that it is the only such capability, and it is now known that at least one more transporter, viz SLC22A15 [ 109 ], can also catalyse ergothioneine uptake.…”

Section: Introductionmentioning

confidence: 99%

The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

Kell

2021

Molecules

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Over the years, my colleagues and I have come to realise that the likelihood of pharmaceutical drugs being able to diffuse through whatever unhindered phospholipid bilayer may exist in intact biological membranes in vivo is vanishingly low. This is because (i) most real biomembranes are mostly protein, not lipid, (ii) unlike purely lipid bilayers that can form transient aqueous channels, the high concentrations of proteins serve to stop such activity, (iii) natural evolution long ago selected against transport methods that just let any undesirable products enter a cell, (iv) transporters have now been identified for all kinds of molecules (even water) that were once thought not to require them, (v) many experiments show a massive variation in the uptake of drugs between different cells, tissues, and organisms, that cannot be explained if lipid bilayer transport is significant or if efflux were the only differentiator, and (vi) many experiments that manipulate the expression level of individual transporters as an independent variable demonstrate their role in drug and nutrient uptake (including in cytotoxicity or adverse drug reactions). This makes such transporters valuable both as a means of targeting drugs (not least anti-infectives) to selected cells or tissues and also as drug targets. The same considerations apply to the exploitation of substrate uptake and product efflux transporters in biotechnology. We are also beginning to recognise that transporters are more promiscuous, and antiporter activity is much more widespread, than had been realised, and that such processes are adaptive (i.e., were selected by natural evolution). The purpose of the present review is to summarise the above, and to rehearse and update readers on recent developments. These developments lead us to retain and indeed to strengthen our contention that for transmembrane pharmaceutical drug transport “phospholipid bilayer transport is negligible”.

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Ergothioneine, recent developments

Cited by 111 publications

References 162 publications

Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study

The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

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