ergothioneine

Ergothionine (EGT) is a compound discovered in 1909, originally found in a fungus Claviceps purpurea. The pure product is white crystals, water-soluble (soluble at room temperature at 0.9 mol/L), and does not self oxidize at physiological pH and in strong alkaline solutions. It exists in two isomers, namely thiol and thione, as shown in the figure on the right.
Ergothionein is a natural antioxidant that can protect cells in the human body and is an important active substance in the body. Natural antioxidants are safe, non-toxic, and have become a hot research topic. As a natural antioxidant, ergothionein has entered people's field of vision. It has various physiological functions such as clearing free radicals, detoxification, maintaining DNA biosynthesis, normal cell growth, and cellular immunity.

Due to its significant and unique biological functions, ergot sulfur has been studied by scholars from various countries for a long time. Although further research is needed, it has provided great inspiration for its application in various fields. Ergothionein has a wide range of applications and market prospects in fields such as organ transplantation, cell preservation, medicine, food and beverage, functional foods, animal feed, cosmetics, and biotechnology.
Used as a unique antioxidant
Ergothionein is a highly protective and non-toxic natural antioxidant that is not easily oxidized in water. This allows its concentration in certain tissues to reach mmol and stimulates the natural antioxidant defense system of cells. Among numerous antioxidants, ergotamine is particularly unique because it can chelate heavy metal ions, which can protect red blood cells in the body from free radical damage.
Used for organ transplantation
The amount and duration of preservation of existing tissues play a decisive role in the success of organ transplantation surgery. The most commonly used antioxidant for organ transplantation is glutathione, which is highly susceptible to oxidation when exposed to the environment. Even in refrigerated or liquid environments, its antioxidant capacity is greatly reduced, causing toxicity to cells and inflammation, inducing the hydrolysis of tissue proteins. And ergothionein is like an antioxidant that is stable in aqueous solution and can chelate heavy metal ions. It can be used as a substitute for glutathione in the field of organ protection, better achieving the protection of transplanted organs.
Add to cosmetics as a skin protectant
The ultraviolet rays UVA in sunlight can penetrate into the dermis layer of human skin, affecting the growth of epidermal cells, causing surface cells to age and die, leading to premature aging of the skin, while ultraviolet UVB is more likely to cause skin cancer. Ergothionein can minimize the formation of reactive oxygen species and protect cells from radiation damage. Therefore, ergothionein can be added as a skin protectant to certain cosmetics for the development of outdoor skincare products and protective cosmetics.
Application in ophthalmology
Research has found that ergotamine plays a crucial role in protecting the eyes, so many researchers hope to develop an ophthalmic product to promote the development of ophthalmic treatment surgery. Ophthalmic surgery is generally performed locally, and the water solubility and stability of ergotamine provide feasibility for such surgery and have great practical value.
In other applications
Due to its excellent properties, ergothionein can be applied in many fields. For example, used in the fields of medicine, food, health products, cosmetics, etc. In the field of medicine, it can be used to treat inflammation and can be made into tablets, capsules, oral preparations, etc; In the field of health products, it can prevent the occurrence of cancer, and can be made into functional foods, functional drinks, and other products. In the field of cosmetics, it can be used for anti-aging and can be made into sunscreen and other products.
With the increasing awareness of health care among people, the excellent properties of ergotamine as a natural antioxidant will gradually be widely recognized and applied.

Product Name:	L-(+)-Ergothioneine
Synonyms:	L-(+)-ERGOTHIONEINE INNER SALT;ERGOLD;2-MERCAPTOHISTIDINE BETAINE;(S)-ALPHA-CARBOXY-2,3-DIHYDRO-N,N,N-TRIMETHYL-2-THIOXO-1H-IMIDAZOLE-4-ETHANAMINIUM INNER SALT;THIONEINE;(S)-[1-carboxy-2-(2-mercaptoimidazol-4-yl)ethyl]trimethylammonium hydroxide;1H-Imidazole-4-ethanaminium, .alpha.-carboxy-2,3-dihydro-N,N,N-trimethyl-2-thioxo-, inner salt, (.alpha.S)-;3-(2-sulfanylidene-1,3-dihydroimidazol-4-yl)-2-trimethylammonio-propanoate
CAS:	497-30-3
MF:	C9H15N3O2S
MW:	229.3
EINECS:	207-843-5
Product Categories:	Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;cosmetics
Mol File:	497-30-3.mol

Description	L-(+)-Ergothioneine is a naturally-occurring amino acid derived from histidine via hercynine. Ergothioneine is a stable antioxidant that scavenges and detoxifies free radicals and oxidants, increases intracellular thiol levels, controls nuclear factor-κB activation, and inhibits inflammatory gene expression. In addition, it inhibits the peroxynitrite-dependent nitration of nitrotyrosine, blocks oxidative DNA damage and cell death, and prevents the formation of xanthine and hypoxanthine. Ergothioneine is transported by the organic cation/carnitine transporter 1, which has been linked with autoimmune diseases, including rheumatoid arthritis and Crohn’s disease.
Chemical Properties	White Solid
Uses	L-(+)-Ergothioneine is a natural molecule isolated from the rye ergot fungus and later identified in rat erythrocytes and liver and in numerous other animal tissues. Its antioxidizing properties may afford the compound therapeutic potential or it may be used as a food additive or in cosmetics.
Definition	ChEBI: Ergothioneine is a L-histidine derivative that is N(alpha),N(alpha),N(alpha)-trimethyl-L-histidine in which the hydrogen at position 2 on the imdazole ring is replaced by a mercapto group. A naturally occurring metabolite of histidine synthesized by bacteria and fungi with antioxidant properties. It is found ubiquitously in plants and animals and is present in many human foodstuffs. It has a role as an antioxidant, a fungal metabolite, a plant metabolite, a xenobiotic metabolite and a chelator. It is an amino-acid betaine, a L-histidine derivative and a sulfur-containing amino acid. It is a conjugate base of an ergothioneine(1+). It is a tautomer of an ergothioneine thione form.
Origin	Ergothioneine was discovered in 1909 by Charles Tanret, a French pharmacist and chemist. Tanret was examining the ergot fungus, which had recently been responsible for destroying crops, and he discovered the compound by using a purification process. The amino acid name ergothioneine originates from this fungus. Though this discovery is relatively recent, scientists speculate that ergothioneine may have originated from ancient earth. Due to its anaerobic nature (it does not require oxygen to function), it may have manifested in the earth's oxygen-free atmosphere more than three billion years ago While ergothioneine is not classified as one of the nine essential amino acids.
benefits	L-(+)-Ergothioneine is a natural antioxidant, which has various physiological functions such as scavenging free radicals, detoxification, maintaining DNA biosynthesis, normal cell growth and cellular immunity.
General Description	L-(+)-Ergothioneine (ERG) is a substance that cannot be synthesized by humans and must be obtained from food. It has cytoprotective and antioxidant properties.
General Description	L-(+)-Ergothioneine (ET) is a sulfur-containing amino acid, which is only produced by Actinomycetales bacteria and non-yeast like fungi belonging to the division Basidiomycota and Ascomycota. It was originally isolated from Claviceps purpurea or rye ergot. It is obtained from L-histidine, which is converted into betaine form called hercynine. It is found in both animals and plants, and mammals usually obtain it from their diet, e.g. through mushrooms or oats. It is tautomeric in nature, and in neutral aqueous solution exists in thione form.
Biochem/physiol Actions	L-(+)-Ergothioneine (ET) has the maximum concentrations in tissues subjected to oxidative stress, with the highest being in blood, eye lens, bone marrow, semen and liver. It acts as an anti-oxidant and prevents apoptosis, by scavenging reactive oxygen and nitrogen species. The anti-oxidant activity is attributable to sulfhydryl groups. It acts as a substrate for SLC22A4 (solute carrier family 22, member 4) transporter. In alveolar macrophages, it prevents the release of interleukin-8 (IL-8) by tumor necrosis factor (TNF)α. IL-8 is an inflammatory cytokine. It also regulates the oxidative damage in liver and kidneys, and has a protective action against lipid peroxidation. It is also responsible for the conservation of endogenous glutathione and α-tocopherol. ET being an antioxidant, protects against γ and UV radiation. In UV-irradiated human dermal fibroblasts, it scavenges reactive oxygen species (ROS), and suppresses matrix metalloproteinases 1 (MMP1) expression. It might also have anti-ageing effects on skin caused by UV-radiation.
Synthesis	The synthesis of L-(+)-Ergothioneine (ET; marketed as Ergoneine®) is performed in water and includes the following steps. First, l-hercynine is reacted with bromine and then with cysteine. The intermediate obtained is transformed into ET by heating in the presence of mercaptopropionic acid. Finally, the raw product is purified by crystallisation.
Synthesis	L-(+)-Ergothioneine is prepared by the reaction of hercynine. The steps are as follows: 15g of compound was added to 150ml of water, and 15.6g of concentrated hydrochloric acid was added, add 10.9g dibromohydantoin, stir for 20min, add D-cysteine, Continue to stir for 1 hour, add sodium thiosulfate, raise the temperature to 90-100°C, and continue the reaction for 15 hours. After the reaction, cool down and filter, adjust the pH to neutral, desalt, concentrate, crystallize with 5ml of water and 75ml of isopropanol, and dissolve the solid Filter and dry at 70-80°C to obtain 88% ergothioneine product with a yield of 81%.
References	[1] Williamson R, et al. L-(+)-Ergothioneine Significantly Improves the Clinical Characteristics of Preeclampsia in the Reduced Uterine Perfusion Pressure Rat Model. Hypertension , 2022; 75. [2] Hoek S, et al. Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine. Frontiers in Bioengineering and Biotechnology, 2019.

biological function
Antioxidant effect
Ergothionein is a natural amino acid derived from plants and can accumulate in animals. Studies have shown that it has antioxidant properties. It can effectively clear - OH, chelate divalent iron and copper ions, prevent H2O2 from generating - OH under the action of iron or copper ions, and inhibit the oxidation of copper dependent oxygenated hemoglobin. It can also inhibit the peroxidation reaction of arachidonic acid that occurs when myoglobin (or hemoglobin) is mixed with H2O2. Ergothionein can also strongly scavenge hypochlorous acid, thereby preventing the inactivation of A1- antiprotease. However, it cannot inhibit the peroxidation reaction of lipid particles in the presence of iron ions. AKanmu D et al. found that a certain concentration of ergothionein can act as an antioxidant in the body.
Protective effect on cells
Ergothionein is a powerful hypochlorous acid scavenger (HOCl), and although many compounds can react with hypochlorous acid, few can react as rapidly as ergothionein. A1- Anti protease inhibitors (APIs), such as elastase, are particularly sensitive to hypochlorous acid, and physiological concentrations of ergotamine can effectively protect APIs against inactivation caused by hypochlorous acid. As neutrophils are the main source of hypochlorous acid in the body, one of the functions of ergotamine is to protect red blood cells from harm from neutrophils in normal functioning or pathological inflammatory sites.
anti-inflammatory effect
Peroxynitrite is the endogenous formation of the limited diffusion reaction of NO and superoxide, and is a strong oxidant related to the pathophysiology of inflammation, such as ischemia reperfusion injury, atherosclerosis, acute pneumonia and sepsis. Ergothionein can inhibit amino acid oxidation mediated by peroxynitrite anions, such as tyrosine nitration, thus providing feasibility for the treatment of inflammation.
Other biological functions
Since the discovery of ergothionein, many people have attempted to explain its physiological functions, but none have been able to fully define its physiological functions. Brummel. m.c's research found that ergothionein may also have the following functions: catalytic action for transporting cations and carbon dioxide carboxylation or decarboxylation reactions; Regulating thyroid and anti thyroid effects; Regulating histamine or antihistamine effects; Choline like function or anti parasympathetic neurophysiological effects; It can regulate the reaction activity of other acyl carriers or act as an acid based carrier itself. Epand R M et al also studied the effect of ergotin on diabetes.
It has strong antioxidant activity: clearing reactive oxygen species, chelating divalent metal ions, activating antioxidant enzymes, inhibiting superoxide dismutase, and inhibiting oxidation reactions of various heme proteins. Due to these characteristics of ergothionein, it has a wide range of applications and market prospects in fields such as medicine, food and beverage, functional foods, animal feed, cosmetics, and biotechnology.
the new supersedes the old
Studies have shown that ergothionein cannot be synthesized in animal bodies, but it has been clearly demonstrated in plants and microorganisms that histidine, the sulforam, and the methyl groups of methionine can be incorporated into ergothionein. D. Yanasugondha and M D. Appleman studied the catabolism of ergothionein in microorganisms and found that ergothionein can be converted into trimethylamine and mercaptan imidazolium acrylic acid; Heath [3] found that ergothionein labeled with [S] was distributed in the bone marrow, red blood cells, liver, kidneys, and other parts of rats after feeding them with food containing [S] ergothionein for 21 days. George Wolf et al. first injected [α - S] ergotamine into mice, and then studied the distribution of radioactive energy and its metabolites. It has been proven that herzynine is a precursor for the synthesis of ergothionein.