Food‐derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice

Nakamichi, Noritaka; Nakayama, Keigo; Ishimoto, Takahiro; Masuo, Yusuke; Wakayama, Tomohiko; Sekiguchi, Hirotaka; Sutoh, Keita; Usumi, Koji; Iseki, Shoichi; Kato, Yukio

doi:10.1002/brb3.477

Cited by 73 publications

(65 citation statements)

References 34 publications

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“…6,43) The K m values for ERGO of OCTN1 obtained in human embryonic kidney 293 cells overexpressing mouse and human OCTN1 were 4.68 and 21 µM, respectively. 6,44) In peripheral organs, OCTN1 gene mutation is associated with susceptibility to Crohn's disease and rheumatoid arthritis, 6,8,9) strongly suggesting that OCTN1 may play a role in these inflammatory disorders.…”

Section: )mentioning

confidence: 99%

“…35) Taken together, the induction of OCTN1 and/or the ingestion of ERGO are conceivable as treatments for neurological disorders associated with OCTN1. We have recently reported that ERGO is highly distributed into the brain after the oral ingestion of an ERGO-containing diet, promotes neuronal differentiation, and exerts an antidepressant-like effect in mice 43) (Fig. 3).…”

Section: )mentioning

confidence: 99%

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Physiological Roles of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Neural Cells

Nakamichi

Kato

2017

Biological & Pharmaceutical Bulletin

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Dysfunction in neurotransmission mediated by neurotransmitters causes various neurological disorders.Therefore, receptors and reuptake transporters of neurotransmitters have been focused on as a therapeutic target in neurological disorders. These membrane proteins have high affinity for a specific neurotransmitter and are highly expressed on synaptic membranes. In contrast, xenobiotic transporters have relatively lower affinity for neurotransmitters but widely recognize various organic cations and/or anions and are also expressed in brain neurons. However, it has been largely unknown why such xenobiotic transporters are expressed in neurons that play a key role in signal transduction. We have therefore attempted to clarify the physiological roles of one such xenobiotic organic cation transporter (OCT) in neural cells with the aim of obtaining new insight into the treatment of neurological disorders. Carnitine/organic cation transporter OCTN1/SLC22A4 is functionally expressed in neurons and neural stem cells. In particular, OCTN1 is expressed at much higher levels compared with other OCTs in neural stem cells and positively regulates their differentiation into neurons. OCTN1 accepts the naturally occurring food-derived antioxidant ergothioneine (ERGO) as a good in vivo substrate. Because ERGO is highly distributed into the brain after oral ingestion, OCTN1 may contribute to the alleviation of oxidative stress and promotion of neuronal differentiation via the uptake of ERGO in the brain, perhaps abating symptoms of neurological disorders. In this review, we introduce current topics on the physiological roles of OCTs with a focus on OCTN1 in neural cells and discuss its possible application to the treatment of neurological disorders.

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Section: )mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Physiological Roles of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Neural Cells

Nakamichi

Kato

2017

Biological & Pharmaceutical Bulletin

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“…Brain and serum ERG levels are also markedly different in Parkinson's disease (515) , reviewed in Hang et al (516) , Shao & Le (517) and Shah & Duda (518) , and even in sudden infant death syndrome (519) , and ERG has been shown to be protective against β-amyloid-induced neuronal injury (520) and cytotoxicity (521) . It can also act as an antidepressant (522) . The evidence for this comes from direct studies (520) and feeding experiments (522) in mice, as well as via the reduction of β-amyloid peptide in a transgenic C. elegans model (521) .…”

Section: Neurological Diseases and Cognitive Functionmentioning

confidence: 99%

“…It can also act as an antidepressant (522) . The evidence for this comes from direct studies (520) and feeding experiments (522) in mice, as well as via the reduction of β-amyloid peptide in a transgenic C. elegans model (521) . As mentioned above, SLC22A4 polymorphisms are associated with ischaemic stroke (417) .…”

Section: Neurological Diseases and Cognitive Functionmentioning

confidence: 99%

The biology of ergothioneine, an antioxidant nutraceutical

et al. 2020

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Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

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“…Ergothioneine can also protect against Aβ-induced memory impairment in mice by exhibiting antioxidative, anti-acetylcholinesterase activities in the brain lysates of Aβ1-40-treated mice [59]. Orally ingested ergothioneine promoted neuronal differentiation and readily permeated the BBB, thus alleviating the symptoms of depression in mice [60]. The structures of uridine (41) and ergothioneine (42) are shown in ▶ Fig.…”

Section: Pleurotus Giganteusmentioning

confidence: 99%

A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders

Yadav

Jeewon

et al. 2020

Planta Med

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According to the World Health Organization, neurological and neurodegenerative diseases are highly debilitating and pose the greatest threats to public health. Diseases of the nervous system are caused by a particular pathological process that negatively affects the central and peripheral nervous systems. These diseases also lead to the loss of neuronal cell function, which causes alterations in the nervous system structure, resulting in the degeneration or death of nerve cells throughout the body. This causes problems with movement (ataxia) and mental dysfunction (dementia), both of which are commonly observed symptoms in Alzheimerʼs disease, Parkinsonʼs disease, Huntingtonʼs disease, and multiple sclerosis. Medicinal mushrooms are higher fungi with nutraceutical properties and are low in calories and fat. They are also a rich source of nutrients and bioactive compounds such as carbohydrates, proteins, fibers, and vitamins that have been used in the treatment of many ailments. Medicinal mushrooms such as Pleurotus giganteus, Ganoderma lucidium, and Hericium erinaceus are commonly produced worldwide for use as health supplements and medicine. Medicinal mushrooms and their extracts have a large number of bioactive compounds, such as polysaccharide β-glucan, or polysaccharide-protein complexes, like lectins, lactones, terpenoids, alkaloids, antibiotics, and metal-chelating agents. This review will focus on the role of the medicinal properties of different medicinal mushrooms that contain bioactive compounds with a protective effect against neuronal dysfunction. This information will facilitate the development of drugs against neurodegenerative diseases.

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Food‐derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice

Cited by 73 publications

References 34 publications

Physiological Roles of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Neural Cells

Physiological Roles of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Neural Cells

The biology of ergothioneine, an antioxidant nutraceutical

A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders

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