Safe and Effective Antioxidant: The Biological Mechanism and Potential Pathways of Ergothioneine in the Skin

Abstract

Ergothioneine, a sulfur-containing micromolecular histidine derivative, has attracted increasing attention from scholars since it was confirmed in the human body. In the human body, ergothioneine is transported and accumulated specifically through OCTN−1, especially in the mitochondria and nucleus, suggesting that it can target damaged cells and tissues as an antioxidant. It shows excellent antioxidant, anti-inflammatory effects, and anti-aging properties, and inhibits melanin production. It is a mega antioxidant that may participate in the antioxidant network system and promote the reducing glutathione regeneration cycle. This review summarizes studies on the antioxidant effects of ergothioneine on various free radicals in vitro to date and systematically introduces its biological activities and potential mechanisms, mostly in dermatology. Additionally, the application of ergothioneine in cosmetics is briefly summarized. Lastly, we propose some problems that require solutions to understand the mechanism of action of ergothioneine. We believe that ergothioneine has good prospects in the food and cosmetics industries, and can thus meet some needs of the health and beauty industry.

The Glutathione System: A Journey from Cyanobacteria to Higher Eukaryotes

“…In some organisms, such as mycobacteria [ 135 ], the γ-glutamyl-cysteine peptide is also used for the synthesis of ergothioneine (hereafter EGT), an unusual thio-histidine betaine amino acid (also known as 2-mercaptohistidine trimethylbetaine) that has potent antioxidant and cytoprotective activities [ 136 , 137 , 138 , 139 , 140 ]. Hence, in mycobacteria there is competition between EGT and glutathione biosynthesis.…”

“…Hence, in mycobacteria there is competition between EGT and glutathione biosynthesis. EGT has both a thiol (antioxidant) and a thione form [ 136 , 140 ], with the latter thione tautomer being predominant at physiological pH, thereby making EGT unusually resistant to oxidation by molecular O 2 [ 137 ]. Its midpoint potential, +0.06 V, is unusually high compared to typical thiols, including GST (−0.2 to −0.4 V) [ 137 ].…”

“…EGT is stable in the body for a long time after ingestion, and is viewed as protecting the central nervous system against diseases [ 138 ]. Animals have evolved a highly selective transporter for it, originally known as a carnitine transporter (OCTN1) [ 138 , 140 ] and also called ergothioneine transporter ETT because of its 100-fold higher affinity for EGT [ 139 ]. Genetic analysis in mycobacteria [ 142 ] and EGT consumption in mammals has shown that EGT protects cells against oxidative [ 137 , 139 ], metal [ 143 ] and UV [ 137 , 139 ] stresses.…”

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

“…Its advantages are low toxicity generally, fewer side effects, and a lack of redox activity [84]. This unique chemical feature of being redox-inactive creates an antioxidant protection system [85]. This divalent zinc ion Zn2+ has an electron affinity that is similar to but not identical to that of the copper ion Cu2+, which eliminates the possibility of free radical reactions [86][87].…”

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

“…Its advantages are low toxicity generally, fewer side effects, and a lack of redox activity [ 81 ]. This unique chemical feature of being redox-inactive creates an antioxidant protection system [ 82 ]. This divalent zinc ion Zn 2+ has an electron affinity that is similar to but not identical to that of the copper ion Cu 2+ , which eliminates the possibility of free radical reactions [ 83 , 84 ].…”