Protective Effect of Ergothioneine Against Stroke in Rodent Models

Ong, Wei‐Yi; Kao, Mei-Han; Cheung, Wai-Mui; Leow, Damien Meng-Kiat; Cheah, Irwin K.; Lin, Teng-Nan

doi:10.1007/s12017-022-08727-w

Cited by 6 publications

(7 citation statements)

References 47 publications

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“…VHCL inhibited the protective effect of ET on mitochondrial dysfunction. Our results add to previous findings that ET has neuroprotective functions [26,72,73] which could potentially aid in the prevention and treatment of PD. We would also like to acknowledge the paper that was published by Yuzawa et al (2024) [73], while we were preparing this manuscript.…”

Section: Discussionsupporting

confidence: 86%

“…It can cross the blood-brain barrier (BBB) and accumulate in the brain following oral administration to mice [24], and is also found in human brain [19,22,25]. ET has shown protective effects against oxidative damage by oxysterols in human brain endothelial cells [26,27], in animal models of stroke [28], cardiovascular disease [29,30], inflammation [31,32], cognitive impairment and dementia in mice [33][34][35], and aging [36]. ET levels in the blood are lower in PD patients [37].…”

Section: Introductionmentioning

confidence: 99%

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Ergothioneine Mediated Neuroprotection of Human iPSC derived-Dopaminergic Neurons.

Leow,

Cheah,

Chen

et al. 2024

Preprint

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Oxidative stress-mediated cell death is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson’s disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson's disease. In this study, we investigated the protective effect of ET on 6-OHDA treated iPSC-derived dopaminergic neurons (iDAs) and further confirmed the protective effects in 6-OHDA treated human neuroblastoma SH-SY5Y cells. In 6-OHDA treated cells, metabolic stress in the form of decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mROS), reduced cellular ATP levels, and increased total protein carbonylation levels was observed. 6-OHDA treatment also significantly decreased tyrosine hydroxylase levels. These effects were significantly abrogated when ET was present. Verapamil hydrochloride (VHCL), a non-specific inhibitor of the ET transporter, OCTN1, abolished ET’s cytoprotective effects, indicative of an intracellular action. These results suggest that ET could be a potential therapeutic for Parkinson’s disease.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Ergothioneine Mediated Neuroprotection of Human iPSC derived-Dopaminergic Neurons.

Leow,

Cheah,

Chen

et al. 2024

Preprint

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“…As already described, ergothioneine is effective against animal models of Alzheimer's disease and stroke by exerting antioxidant and neuroprotective effects [17,18]. Neuroprotective effects of ergothioneine have also been reported in studies using cultured cells.…”

Section: Discussionmentioning

confidence: 78%

“…Furthermore, another group analyzed the efficacy of intracerebroventricular or intraperitoneal administration of ergothioneine in a rat stroke model. They found that ergothioneine significantly reduced cerebral infarct volume with both methods of administration, while MRI analysis revealed that ergothioneine had neuroprotective effects in the stroke model [18].…”

Section: Introductionmentioning

confidence: 99%

Ergothioneine Prevents Neuronal Cell Death Caused by the Neurotoxin 6-Hydroxydopamine

Yuzawa,

Nakashio,

Ichimura

et al. 2024

Cells

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Neuronal cell death is a key mechanism involved in the development and exacerbation of Parkinson’s disease (PD). The excessive production of reactive oxygen species (ROS) is a major cause leading to neuronal death; therefore, compounds that prevent oxidative stress-dependent neuronal death may be promising as a preventive method for PD. Ergothioneine is a natural amino acid with antioxidant properties, and its protective functions in the body are attracting attention. However, there has been no investigation into the protective functions of ergothioneine using in vivo and in vitro PD models. Thus, in this study, we analyzed the efficacy of ergothioneine against 6-hydroxydopamine (6-OHDA)-dependent neuronal cell death using immortalized hypothalamic neurons (GT1-7 cells). First, we found that ergothioneine prevents 6-OHDA-dependent neuronal cell death by suppressing ROS overproduction in GT1-7 cells. The cytoprotective effect of ergothioneine was partially abolished by verapamil, an inhibitor of OCTN1, which is involved in ergothioneine uptake. Furthermore, ergothioneine-rich Rice-koji (Ergo-koji) showed cytoprotective and antioxidant effects similar to those of ergothioneine. Taken together, these results suggest that ergothioneine or foods containing ergothioneine may be an effective method for preventing the development and progression of PD.

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“…These results add to our previous findings that 7KC has cytotoxic and proinflammatory effects on brain endothelial cells, which are protected by ET. It is hoped that these results shed light on the role of ET in the prevention and treatment of neurovascular brain disorders, in which we recently showed a neuroprotective effect of ET in rodent models of stroke [ 72 ]. Further studies are needed to elucidate the protective effect of ET against 7KC in vivo.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Ergothioneine against 7-Ketocholesterol-Induced Mitochondrial Damage in hCMEC/D3 Human Brain Endothelial Cells

Leow

Cheah

Fong

et al. 2023

IJMS

Self Cite

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Recent findings have suggested that the natural compound ergothioneine (ET), which is synthesised by certain fungi and bacteria, has considerable cytoprotective potential. We previously demonstrated the anti-inflammatory effects of ET on 7-ketocholesterol (7KC)-induced endothelial injury in human blood-brain barrier endothelial cells (hCMEC/D3). 7KC is an oxidised form of cholesterol present in atheromatous plaques and the sera of patients with hypercholesterolaemia and diabetes mellitus. The aim of this study was to elucidate the protective effect of ET on 7KC-induced mitochondrial damage. Exposure of human brain endothelial cells to 7KC led to a loss of cell viability, together with an increase in intracellular free calcium levels, increased cellular and mitochondrial reactive oxygen species, a decrease in mitochondrial membrane potential, reductions in ATP levels, and increases in mRNA expression of TFAM, Nrf2, IL-1β, IL-6 and IL-8. These effects were significantly decreased by ET. Protective effects of ET were diminished when endothelial cells were coincubated with verapamil hydrochloride (VHCL), a nonspecific inhibitor of the ET transporter OCTN1 (SLC22A4). This outcome demonstrates that ET-mediated protection against 7KC-induced mitochondrial damage occurred intracellularly and not through direct interaction with 7KC. OCTN1 mRNA expression itself was significantly increased in endothelial cells after 7KC treatment, consistent with the notion that stress and injury may increase ET uptake. Our results indicate that ET can protect against 7KC-induced mitochondrial injury in brain endothelial cells.

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Protective Effect of Ergothioneine Against Stroke in Rodent Models

Cited by 6 publications

References 47 publications

Ergothioneine Mediated Neuroprotection of Human iPSC derived-Dopaminergic Neurons.

Ergothioneine Mediated Neuroprotection of Human iPSC derived-Dopaminergic Neurons.

Ergothioneine Prevents Neuronal Cell Death Caused by the Neurotoxin 6-Hydroxydopamine

Protective Effect of Ergothioneine against 7-Ketocholesterol-Induced Mitochondrial Damage in hCMEC/D3 Human Brain Endothelial Cells

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