Ergothioneine. Although it is not as well known as some common nutrients, it plays a vital role in our bodies. Today, let's unravel the mystery of ergothioneine, its past and present, and its amazing scientific mysteries.
Ergothioneine (ergothioneine, EGT) is a compound discovered in 1909, originally discovered in a fungus, Claviceps purpurea, pure is white crystals, water-soluble, (soluble 0.9mol/L at room temperature), and will not self-oxidize at physiological pH and in strong alkali solutions. It exists in two isomers, namely thiol and thione forms, as shown in the figure on the right.
Ergothioneine is a natural antioxidant that can play a protective role in cells in the human body and is an important active substance in the body. Natural antioxidants are safe and non-toxic, and have become a hot topic of research. As a natural antioxidant, ergothioneine has come into people's field of vision, which has a variety of physiological functions such as scavenging free radicals, detoxifying, maintaining DNA biosynthesis, normal cell growth and cellular immunity.
1. Ergothioneine's Past Life: A Tortuous Journey of Discovery
Back in 1909, a scientist named Charles Tanret accidentally discovered ergothioneine while studying the fungus clavicepspurpurea. However, in those days, it was only a small supporting role in ergogram research. At the same time, lysergic acid diethylamide (LSD) attracted a lot of attention from the academic community due to its unique hallucinogenic effect, while ergothioneine was ignored for a long time, silently waiting for the opportunity to be rediscovered.
In the decades after its discovery, the exploration of the properties and functions of ergothioneine was slow due to the limitations of scientific research technology and conditions at that time. Other high-profile substances and research fields occupy scientific research resources and people's attention, so that ergothioneine has not received enough attention and in-depth research for a long time.
But fate is always full of twists and turns. In 2005, the transporter OCTN1, which is expressed almost universally in living organisms, was discovered. Studies have shown that when ergothioneine is ingested, the amount of ergothioneine accumulation available to tissues in the body is directly related to the expression of OCTN1. This important discovery is like a light in the darkness, providing important clues and directions for further research on ergothioneine. Since then, people have begun to pay attention to the absorption, distribution and mechanism of action of ergothioneine in the human body, and the research of ergothioneine has gradually embarked on the right track.
2. The present life of ergothioneine: a high-profile "longevity vitamin"
In 2018, University of California professor Bruce Ames published a landmark paper calling ergothioneine a "longevity vitamin." This designation was like a boulder thrown into a calm lake, and it instantly attracted widespread attention. From 2018 to 2024, the number of related research publications has exploded, and ergothioneine has quickly occupied the front-line position of anti-aging beauty and health products.
Ergothioneine is distributed in some tissues and organs of mammals, mainly in red blood cells (about 1~2 mmol. L) and the semen of some animals, although there are no experimental studies showing that animals can synthesize the substance, there is certainly a pathway for the absorption and retention of ergothioneine in animal cells. In carnivores, ergothioneine in animal tissues can provide dietary needs. Melville, D.B. and Eich. S [1] found that ergothioneine was also present in cereal plants. Subsequent studies by Melville.D.B and Genghof.D.S et al. showed that ergothioneine is a common component of many microbial cells and can be synthesized in several fungi but not in bacteria. In edible mushrooms such as porcini mushrooms, mushrooms, and hairy ghost umbrellas, it can produce the precursor histidine trimethyl salt (hercynine) required for the synthesis of ergothioneine; Moreover, the hairy ghost umbrella can also produce rare amino acids such as ergothioneine.
Ergothioneine has also begun to be added to skin care products of major brands, such as Clinique, La Mer, Tangerine, Proya, etc. The popularity of these skincare products has further boosted the popularity and application of ergothioneine. People are beginning to realize that ergothioneine is not just an ordinary chemical, it can be a key key to opening the door to a long and healthy life.
Ergomyceae
3. A review of scientific research on ergothioneine
There are three preparation methods for ergothioneine: chemical synthesis, extraction and biological fermentation.
It is very difficult to synthesize L-propron ergothioneine by chemical methods, and several synthesis methods have not achieved the expected yield due to partial or total racemization, and the difficulty of synthesis is that it is difficult to prepare the raw material 2-mercaptoimidazole, and the acidity of the α carbon will make the reaction easy to racemic. OXIS International was the first to develop a highly efficient and commercially available method for the synthesis of ergothioneine [2] and patented it in 1995 by introducing sulfhydryl groups into the imidazole ring. However, due to the difficulty in ensuring the safety of chemically synthesized products, the high cost of synthetic raw materials, the high cost of synthesis, and the high selling price of products limit the application of ergothioneine.
The natural biological extraction method is to extract ergothioneine from the fruiting body of edible fungi, pig blood, animal tissues, ergot and grains, but the content of ergothioneine in the above-mentioned raw materials is still very low, and there are many impurities in the raw materials, drug residues, high extraction costs and other problems, which limit the application of ergothioneine and are not suitable for industrialization;
The biosynthesis of ergothioneine by mycelium deep fermentation technology of mushroom fungus is the mainstream direction of low-cost large-scale production of ergothioneine, which can effectively improve the yield of ergothioneine, reduce the production cost, and more importantly, ensure the safety of the product and broaden the application space of ergothioneine.
(1) Antioxidant effect: the guardian of life
Antioxidant effect
Ergothioneine is a natural amino acid derived from plants and can accumulate in animals, and studies have proved that it has the effect of antioxidants, it can effectively remove -OH, can chelate divalent iron ions and copper ions, prevent H2O2 from forming -OH under the action of iron ions or copper ions, and can also inhibit the oxidation of copper-dependent oxyhemoglobin and inhibit the peroxidation reaction that promotes arachidonic acid after myoglobin (or hemoglobin) is mixed with H2O2. Ergothioneine also strongly removes hypochlorous acid, thereby preventing the inactivation of A1-antiprotease. However, it does not inhibit the peroxidation of lipid particles in the presence of iron ions. Akanmu D et al. have shown that the presence of ergothioneine in the body at a certain concentration can act as an antioxidant.
Protective effect on cells
Ergothioneine is a powerful hypochlorous acid scavenger (HOCl), and while many compounds can react with hypochlorous acid, few can react as quickly as ergothioneine. A 1-antiprotease inhibitors (APIs), such as elastase, are particularly sensitive to hypochlorous acid, and physiological concentrations of ergothioneine are very effective in protecting the API against the inactivation caused by hypochlorous acid, since neutrophils are the main source of hypochlorous acid in the body, one of the functions of ergothioneine is to protect red blood cells from neutrophils from normal function or pathological sites of inflammation.
Anti-inflammatory effect
Peroxynitrite is an endogenous formation of limited diffusion of NO and superoxide, and is a strong oxidant involved in the pathophysiology of inflammation, such as ischemia-reperfusion injury, atherosclerosis, acute pneumonia, and sepsis. Ergothioneine inhibits peroxynitrosoanion-mediated oxidation of amino acids, such as tyrosine nitration, thus providing feasibility for the treatment of inflammation.
Other biological functions
Since the discovery of ergothioneine, many attempts have been made to elucidate its physiology, but none have been able to fully define its physiology. The Brummel.m.c study found that ergothioneine may also have the following functions: catalytic effect of cation transport and carbon dioxide carboxylation or decarboxylation, thyroid and antithyroid effect, histamine or antihistamine effect, cholinergoid function or antisympathetic physiological effect; It can regulate the reactivity of other acyl carriers or act as an acid support itself. Epand R M et al. also studied the effect of ergothioneine on diabetes.
It has strong antioxidant activity: scavenging reactive oxygen species, chelating divalent metal ions, activating antioxidant enzymes, inhibiting superoxide dismutase, inhibiting the oxidation reaction of various heme proteins, etc. Due to these characteristics, ergothioneine has a wide range of uses and market prospects in the fields of medicine, food and beverage, functional food, animal feed, cosmetics and biotechnology.
metabolism
研究已表明麦角硫因不能在动物体内合成，但在植物和微生物体内己经明确表明了组氨酸（histidine）、the sulfuratom 、the methyl groups of methionine可以合成(incorporate into)麦角硫因。 D. Yanasugondha和M.D. Appleman研究了麦角硫因在微生物中的分解代谢，他们发现麦角硫因可以转化成三甲胺和硫醇咪唑丙烯酸；Heath [3]在给长鼠长达21天喂养含[S]麦角硫因的食物后，发现带[S]标记的麦角硫因分布于骨髓、红血球、肝脏、肾脏等部位。 而George Wolf 等先将[α-S]麦角硫因注入鼠内，然后研究了放射能的分布及其代谢产物。 证明了herzynine是合成麦角硫因的前体(precursor)。
(2) Anti-aging and longevity: the challenger of time
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Relationship with age
As we age, the amount of ergothioneine in the body gradually decreases. This phenomenon caught the attention of scientists, who began to think about the potential link between ergothioneine and the aging process.
The study also found that ergothioneine levels were also significantly reduced in patients with a variety of aging-related diseases. This suggests that ergothioneine may play an important regulatory role in the aging process. Ergothioneine supplementation may be an effective way to slow down aging.
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Evidence from animal experiments
In order to verify the anti-aging and longevity effect of ergothioneine, scientists have conducted a large number of animal experiments. A study in early 2022 found that after feeding fruit flies a diet containing moderate ergothioneine, the lifespan of fruit flies was somewhat extended, and their reproductive ability was not affected.
Another study in the same year found that telomere length was generally longer and the proportion of short telomerics was significantly lower in cells treated with ergothioneine. Telomere shortening is one of the hallmarks of biological aging, and ergothioneine can effectively reverse this situation, further demonstrating its potential anti-aging and longevity effects.
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Improvement of aging-related diseases
In addition to the anti-aging effect shown in animal experiments, ergothioneine has also shown an improvement effect in aging-related lesions such as eye diseases (such as macular degeneration, etc.), neurological diseases (such as epilepsy, etc.) and cardiovascular diseases (such as cardiometabolic diseases) in the intervention of the elderly.
In terms of eye diseases, ergothioneine can protect retinal cells from oxidative damage and reduce the risk of macular degeneration. In neurological diseases, it may reduce the damage to nerve cells and improve the symptoms of epilepsy and other diseases through antioxidant and anti-inflammatory effects. In cardiovascular disease, ergothioneine can reduce oxidative stress levels, protect the cardiovascular system, and reduce the occurrence of cardiometabolic diseases.
(3) Protective effect on the skin: the guardian of beauty
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Protects against UV damage
The ultraviolet rays in the sun have a great damaging effect on the skin. Ultraviolet rays (UVA) rays can penetrate into the dermis layer of human skin, affecting the growth of epidermal cells, causing surface cells to die of old age and cause premature skin aging. Ultraviolet rays (UVB) rays are more likely to cause skin cancer.
Ergothioneine minimizes the formation of reactive oxygen species and protects cells from radiation damage. Therefore, it can be added to cosmetics as a skin protectant, used to develop outdoor skin care products, as well as protective cosmetics.
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Increases the skin's antioxidant levels
Ergothioneine can increase endogenous antioxidant levels in skin keratinocytes through the NRF2/ARE pathway. NRF2 is an important intracellular antioxidant transcription factor, which regulates the expression of a variety of antioxidant and detoxification enzymes.
When ergothioneine activates NRF2, it strengthens skin cells' antioxidant defenses and protects the skin from oxidative stress. This makes ergothioneine one of the most popular ingredients in skincare products.
(4) Protective effects on reproductive health
Studies have found that a large amount of ergothioneine is enriched in the seminal plasma of animals, suggesting that ergothioneine may have an effect on sperm function in the testicles and seminal vesicles, among other things.
In a study on the infertility side effects of anti-cancer drugs, scientists found that ergothioneine supplementation increased sperm count and motility in rats and reduced sperm abnormalities. In addition, the application of ergothioneine to sperm cryofluid can improve the preservation of frozen sperm.
(5) Other biological functions
Ergothioneine also has certain anti-inflammatory effects, which can inhibit peroxynitrosoanion-mediated oxidation of amino acids, such as tyrosine nitration, thus providing feasibility for the treatment of inflammation.
In addition, some studies have shown that ergothioneine may also have cation transport, thyroid function, histamine or antihistamine regulation, cholinergoid function, or anti-parasympathetic physiological effects. However, further research is needed to confirm these features.
4. Application prospect of ergothioneine
With the deepening of the research on ergothioneine, its application prospect is becoming more and more broad.
In the field of medicine, ergothioneine is expected to be a new drug for the treatment of aging-related diseases. For example, for eye diseases, nervous system diseases, and cardiovascular diseases, the development of drugs with ergothioneine as the main ingredient brings new hope to patients.
In the field of health supplements, ergothioneine can be used as a natural antioxidant to be added to various health products to help people delay aging and improve immunity.
In the field of cosmetics, ergothioneine has become an important ingredient in many high-end skin care products. In the future, with the continuous progress of technology, the application of ergothioneine in cosmetics will be more extensive and deeper.
For the substance of ergothioneone because of its significant and unique biological function, scholars from all over the world have carried out research on its application for a long time, although it needs to be further deepened, but it has played a good role in its application in various fields. Ergothioneine has a wide range of uses and market prospects in the fields of organ transplantation, cell preservation, medicine, food and beverage, functional food, animal feed, cosmetics and biotechnology.
Used as a unique antioxidant
Ergothioneine is a highly protective, non-toxic natural antioxidant that is not easily oxidized in water, which allows them to reach concentrations of mmol in certain tissues and stimulates the cell's natural antioxidant defense system. Among the many antioxidants, ergothioneine is particularly unique because ergothioneine can chelate heavy metal ions, which can protect the body's red blood cells from free radical damage.
It is used in organ transplantation
The amount and duration of existing tissue preservation plays a decisive role in the success of organ transplant surgery. The most common antioxidant used in organ transplantation is glutathione, which is highly oxidized when exposed to the environment, and its antioxidant capacity is greatly reduced even in refrigerated or liquid environments, causing toxicity to cells and causing inflammation, inducing hydrolysis of tissue proteins. Ergothioneine is like an antioxidant that is stable in aqueous solution and can also chelate heavy metal ions, which can be used as a substitute for glutathione in the field of organ protection to better realize the protection of transplanted organs.
It is added to cosmetics as a skin protector
Ultraviolet rays in sunlight can penetrate into the dermis layer of human skin, affecting the growth of epidermal cells, causing surface cells to die of old age, causing premature skin aging, and ultraviolet UVB is more likely to lead to skin cancer. Ergothioneine can be added to some cosmetics as a skin protector to minimize the formation of reactive oxygen species and protect cells from radiation damage, so ergothioneine can be added to some cosmetics as a skin protector for the development of outdoor skin care products and protective cosmetics.
Application in ophthalmology
Ergothioneine has been found to play a key role in eye protection, so many researchers hope to develop an ophthalmic product to facilitate the development of ophthalmic treatments. Ophthalmic surgery is generally performed locally, and the water solubility and stability of ergothioneine provide the feasibility of performing this surgery and have great application value.
In other applications
Ergothioneine can be applied to many fields due to its excellent properties. For example, it is used in the field of medicine, food, health products, cosmetics, etc. In the field of medicine, it can be used to treat inflammation, etc., and can be made into tablets, capsules, oral preparations, etc.; In the field of health supplements, it can be used to prevent the occurrence of cancer, and can be made into functional foods, functional drinks and other products, and in the field of cosmetics, it can be used for anti-aging, and can be made into sunscreens and other products.
V. Conclusions
Ergothioneine, a once neglected substance, is now gradually entering people's field of vision with its powerful antioxidant, anti-aging and longevity, skin and reproductive health protection effects. It is like a silent guardian of our lives, playing an important role in all corners of our bodies.
Although some of the mechanisms of action of ergothioneine are not fully understood, with the continuous deepening of scientific research, we believe that ergothioneine will bring more surprises to human health and beauty. Let us look forward to ergothioneine continuing to bloom more brilliantly in the future development.