How does L-Ergothioneine(CAS: 497-30-3) become a product formula for cosmetics, pharmaceuticals and foods?

SeeBio's L-Ergothioneine (EGT, CAS: 497-30-3) is a rare chiral amino acid with multiple cellular physiological protective functions, including scavenging free radicals, detoxification, maintenance of DNA biosynthesis, promotion of normal cell growth, enhancement of cell immune system, providing anti-radiation, whitening, and anti-aging properties. It has a wide range of applications in cosmetics, biomedicine, functional foods, and other fields and has been included in the EU's new resource food list.

EGT is a rare natural chiral amino acid (a sulfur-containing histidine derivative) with the following chemical structure:

EGT exists in two structural isomers, thione and thiol, in its dissolved state.

Isomerism of Thione and Thiol in L-Ergothioneine

Efficacy of L-Ergothioneine

Powerful Antioxidant:

L-Ergothioneine has long been recognized as a potent low-molecular-weight antioxidant. It enters the human body mainly through dietary intake and can accumulate in cells under conditions of high oxidative stress. Compared to other antioxidants like resveratrol, L-Ergothioneine has higher bioavailability. This is because L-Ergothioneine possesses unique biological characteristics, allowing it to accumulate through the OCTN1 transporter (L-Ergothioneine transporter) in skin cells and tissues. In contrast to most water-soluble antioxidants, L-Ergothioneine cannot penetrate cell membranes but is transported through cells via OCTN1. The antioxidant effects of L-Ergothioneine in the body include direct scavenging of reactive oxygen species, chelation of various divalent metal cations, activation of antioxidant enzymes (such as glutathione reductase and mitochondrial superoxide dismutase), and inhibition of oxidation of hemoglobin (such as hemin and myoglobin).

Inhibition of UV-induced damage and cell apoptosis:

UV radiation activates various growth factor and cell factor receptor-related signaling pathways, leading to damage to DNA, proteins, lipids, and cell apoptosis. L-Ergothioneine has the ability to inhibit the expression of genes induced by UV, such as MMP-1 (mainly degrading type I collagen) and TNF-α (promoting the production of inflammatory factors), thereby reducing the occurrence of these damages. It also possesses anti-photoaging abilities, effectively inhibiting the process of UV-induced DNA, protein, and lipid damage, as well as cell apoptosis.

Application in the Cosmetic Industry

L-Ergothioneine is widely used in cosmetics as an antioxidant, especially in skincare products. It effectively reduces oxidative stress by eliminating free radicals, decreasing skin damage, and signs of aging caused by ultraviolet radiation. EGT enhances the resistance of skin cells, reduces damage to DNA, proteins, and lipids, facilitates DNA repair, increases cell survival rates, and promotes skin health. As a natural antioxidant ingredient, the application of EGT in cosmetics helps protect the skin from environmental stressors, maintaining a youthful and healthy complexion.

Skin Protection: L-Ergothioneine (EGT) is widely used in cosmetics as an antioxidant, especially in skincare products. By scavenging free radicals, it effectively reduces oxidative stress, mitigates skin damage, and decreases signs of aging caused by UV exposure. EGT also enhances the resistance of skin cells, reducing DNA, protein, and lipid damage, aiding in DNA repair, increasing cell survival, and promoting skin health. As a natural antioxidant ingredient, EGT's application in cosmetics helps protect the skin from environmental stressors, maintaining its youthful and healthy appearance.

Preventing UV-induced ROS Damage: L-Ergothioneine (EGT) is a natural antioxidant found in food plants and tissues exposed to relatively high levels of oxidative stress. Compared to coenzyme Q10 as an antioxidant analogue, both are widely used in skincare products, but their relative efficacy has been lacking detailed descriptions. Studies suggest that OCTN-1, a specific receptor/transporter protein for EGT, is present in cultured human fibroblast cells and easily detectable. EGT shows higher efficiency in inhibiting lipid peroxidation compared to coenzyme Q10, and samples treated with EGT exhibit significantly fewer peroxides within 120 minutes after the addition of the antioxidant H2O2 when compared to those treated with coenzyme Q10. Additionally, EGT captures reactive oxygen species (ROS) more rapidly and effectively after exposure to UVA340 irradiation. Thus, due to the presence of OCTN-1 in fibroblast cells, EGT is considered a natural skin antioxidant. Relative to coenzyme Q10 and idebenone, EGT directly eliminates free radicals more efficiently, protecting cells from UV-induced ROS damage.

Delaying Skin Aging: L-Ergothioneine (EGT) is a sulfur-containing amino acid regarded as a natural antioxidant in nature. This unique amino acid has the ability to eliminate free radicals while also protecting cells from oxidative stress induced by UV radiation. In related studies, EGT was found to eliminate superoxide radicals (•O2–) and singlet oxygen (1O2). In cell cultures, EGT successfully inhibited the upregulation of tumor necrosis factor-α (TNF-α) induced by UVB irradiation. Furthermore, EGT significantly inhibited approximately 50% of matrix metalloproteinase-1 (MMP-1) protein expression in fibroblasts exposed to UV-A and reduced the expression levels of MMP-1 mRNA. This study suggests that EGT can eliminate reactive oxygen species generated by type I and type II photosensitization while inhibiting the expression of TNF-α and MMP-1, thereby reducing the aging effects induced by UV radiation.

Skin Care and Anti-Photoaging Ingredient: Changes associated with aging at the cellular level are often closely related to the physiological status of mitochondria. In these changes, a common type of mitochondrial DNA damage is the so-called "common deletion," referring to the loss of 4977 base pairs in mitochondrial DNA. In skin cells, this phenomenon is typically caused by UV-induced oxidative damage to mitochondrial DNA. The aim of the study was to assess the impact of the antioxidant L-Ergothioneine on UV-induced skin cell damage. The study also focused on the influence of L-Ergothioneine on the levels of reduced glutathione and detected the presence of "common deletions" in human fibroblast cells through polymerase chain reaction. The results showed that L-Ergothioneine increased intracellular levels of reduced glutathione and effectively protected cells from UV-induced mitochondrial DNA "common deletions." Considering the overall study results, L-Ergothioneine could be an effective component in skin care and anti-photoaging formulations.

Protecting Epidermal Keratinocytes: L-Ergothioneine has long been considered a potent and stable low-molecular-weight antioxidant. Humans intake L-Ergothioneine through diet, and it accumulates in cells that typically experience high levels of oxidative stress. However, as L-Ergothioneine cannot penetrate cell membranes, its protective function is limited to cells expressing the specific receptor/transporter protein OCTN1 for L-Ergothioneine. It has been observed that epidermal keratinocytes in skin cells also have the ability to synthesize OCTN1, allowing them to internalize and accumulate L-Ergothioneine. This accumulation imparts stronger antioxidant capabilities to cells, reducing levels of reactive oxygen species, DNA, proteins, and lipid damage in epidermal keratinocytes under simulated solar UV oxidative stress. L-Ergothioneine not only prevents oxidative damage but also potentially promotes cell DNA repair under UV radiation. This reduces oxidative damage to cellular components, limits apoptotic responses, and improves cell survival. The ability of cells to absorb, accumulate, and utilize the potent antioxidant L-Ergothioneine makes this natural amino acid and its receptor/transporter protein vital components of the skin's antioxidant defense system.

Application in the Biopharmaceuticals Industry

L-Ergothioneine (EGT) finds extensive applications in the field of biopharmaceuticals. EGT demonstrates potential antioxidant and anti-inflammatory effects, particularly in the treatment of type 2 diabetes and its complications. Studies have indicated that the use of EGT alone or in combination with metformin can reduce kidney and liver damage, improve blood glucose control, decrease oxidative stress, and mitigate inflammatory responses, offering potential relief from complications associated with type 2 diabetes. Further research is still needed to address issues such as the therapeutic dosage of EGT, the regulatory mechanisms of the OCTN1 receptor, and its impact on intestinal microbiota.

Potential Antioxidant and Anti-Inflammatory Effects: L-Ergothioneine (EGT) finds extensive application in the biopharmaceutical field, showing potential antioxidant and anti-inflammatory effects, especially in the treatment of type 2 diabetes and its complications. Research indicates that EGT, either alone or in combination with metformin, can reduce kidney and liver damage, improve blood glucose control, decrease oxidative stress and inflammatory responses, potentially alleviating complications associated with type 2 diabetes. Further research is needed to address issues such as the therapeutic dosage of EGT, the regulatory mechanisms of the OCTN1 receptor, and its impact on gut microbiota.

Alleviating Renal Function Impairment: L-Ergothioneine (L-EGT) is an approved supplement by the Food and Drug Administration (FDA), possessing cellular protection, antioxidant, and anti-inflammatory properties. A study investigated its renal protective effect in a rat model of type 2 diabetes (T2D), assessing the protective effects of L-EGT alone or in combination with metformin on renal damage in a T2D rat model induced by fructose-streptozotocin. The results demonstrated that L-EGT, alone or in combination with metformin, could alleviate renal function impairment, lower hyperglycemia, improve therapeutic effects, and enhance the expression of antioxidant and anti-inflammatory genes. Therefore, the combined use of L-EGT and metformin may serve as an adjunct therapy for alleviating renal damage in type 2 diabetes.

Treatment of Hepatic Complications: A study evaluated the hepatoprotective effects of L-Ergothioneine (L-EGT) alone and in combination with metformin in rats with type 2 diabetes (T2D). The results indicated that L-EGT alone or in combination with metformin could reduce liver enlargement, liver damage, triglyceride levels, oxidative stress, and inflammation in rats with T2D. Additionally, the co-administration of L-EGT and metformin in diabetic rats led to a reduction in blood glucose and insulin resistance. These research findings support the potential role of L-EGT in the treatment of liver complications associated with T2D.

Addressing UV-Induced Cellular Responses: Ergothioneine (EGT), a sulfur-containing amino acid, is considered to have natural antioxidant properties. The aim of this study was to determine the nature of its antioxidant activity and investigate the impact of EGT on UV-induced cellular responses. In chemical studies, EGT scavenged superoxide anion radicals (O-2(-)) and singlet oxygen (O-1(2)). In cultured fibroblast cells, EGT inhibited the upregulation of TNF-α following UVB irradiation. Furthermore, in fibroblast cells exposed to UV-A, EGT inhibited the expression of matrix metalloproteinase-1 (MMP-1) protein by nearly 50% and reduced the expression of MMP-1 mRNA. From these results, it can be concluded that EGT clears reactive oxygen species generated by type I and type II photosensitization and inhibits the transcriptional expression of TNF-α and MMP-1. EGT may reduce the anti-aging effects of skin after UV radiation by clearing O-2(-) and O-1(2), thereby limiting the signals of proteases and inflammation activity.

Preventing Oxidative Stress-Related Diseases: Ergothioneine (EGT), as a natural antioxidant, has shown remarkable potential in the treatment or prevention of oxidative stress-related diseases. Its antioxidant function is significantly superior to other natural antioxidants. Despite widespread use in the pharmaceutical and cosmetic industries, challenges still exist in the application of EGT. These challenges include researching other potentially beneficial components in mushrooms, clarifying the relationship between the therapeutic dosage of EGT and diseases, exploring the regulatory mechanisms of OCTN1 expression, and revealing other potential mechanisms of action for EGT. Additionally, more research is needed to understand the impact of EGT on gut microbiota.

Food Industry Applications:

Ergothioneine (EGT) has obtained novel food approval in Europe, confirming its safety in the food industry. Relevant studies have estimated the daily intake of EGT from novel foods in various age groups, and the results indicate levels below the established safe threshold (NOAEL). Furthermore, research highlights the preventive effects of EGT on embryonic development abnormalities in diabetic pregnant mice, supporting its use as an indicator for milk heat treatment. This series of research findings solidify the position of EGT as a safe and effective ingredient in the field of food.

L-Ergothioneine has obtained Novel Food approval in Europe, demonstrating its safety in the food industry. Studies have estimated the daily intake of L-Ergothioneine from Novel Foods for various age groups, finding it to be below the no-observed-adverse-effect level (NOAEL). Furthermore, research highlights the preventive effects of L-Ergothioneine on embryonic development abnormalities in diabetic pregnant mice and supports its use as an indicator for milk heat treatment. These studies affirm the status of L-Ergothioneine as a safe and effective ingredient in the food industry.

In response to the European Commission's request, the Panel on Dietetic Products, Nutrition, and Allergies (NDA) assessed the supplementary dietary intake and safety of synthetic L-Ergothioneine as a Novel Food. The committee estimated the maximum daily intake of L-Ergothioneine from Novel Foods for various population groups, in addition to background dietary intake. The results indicated that the proposed use of synthetic L-Ergothioneine in Novel Foods for infants, children, and adults (including pregnant and lactating women) is safe. The safety margins were considered large enough for infants (284), children (236), and adults (including pregnant and lactating women, with a margin of 610). Therefore, the committee concluded that the proposed use of synthetic L-Ergothioneine as a Novel Food is safe for infants, children, pregnant women, and lactating women.

Reproductive Safety Studies: Reproductive safety of naturally occurring L-Ergothioneine was evaluated in rats through dietary intake. Daily supplementation of diabetic pregnant rats with 1.147 mg/kg body weight of L-Ergothioneine during the first 10 weeks of pregnancy reduced the incidence of embryo malformations, approaching levels observed in non-diabetic animals. L-Ergothioneine did not affect plasma glucose levels in diabetic and control animals. The conclusion drawn was that L-Ergothioneine plays a crucial role in antioxidant prevention by inhibiting glucose-mediated free radical-dependent embryonic malformations, potentially assisting in managing diabetes-induced embryonic lesions, especially when combined with vitamin E.

Impact on Embryonic Development: The study investigated the effects of the natural antioxidant ergothioneine on embryonic development abnormalities in diabetic pregnant mice. Supplementation of 1.147 mg/kg body weight of L-Ergothioneine to diabetic pregnant mice for only the first 11.5 days of pregnancy successfully reduced the incidence of embryonic malformations to levels similar to non-diabetic animals. L-Ergothioneine had no impact on plasma glucose levels in both diabetic and control animals. The conclusion was that L-Ergothioneine plays a crucial role in antioxidant prevention by inhibiting glucose-mediated free radical-dependent embryonic malformations, potentially assisting in managing diabetes-induced embryonic lesions, especially when combined with vitamin E.

Indicator for Milk Heat Treatment: A highly efficient and sensitive high-performance liquid chromatography (HILIC-UPLC) method was developed to determine L-Ergothioneine (ERT) in commercial milk. After derivatization of ERT, chromatographic separation was achieved using a Waters Cortecs UPLC HILIC 1.6 μm column with a mixture of 30 mmol/L ammonium acetate/acetonitrile (10:90, v/v) as the isocratic mobile phase, in less than 5 minutes. The detection and quantification limits were 0.03 and 0.10 μmol/L, respectively. The method exhibited linearity in the concentration range of 0.16 to 5.08 μmol/L. The average detected concentration of ERT in different categories of commercial milk was 0.442 ± 0.191 μmol/L, with the highest content in ultra-high-temperature-treated milk and lower levels in untreated and high-temperature short-time full-fat milk. The study suggests that ERT can serve as an indicator for milk heat treatment.

L-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Recent research has investigated its toxicology and mutagenic potential, with results indicating that L-(+) Ergothioneine and its natural biomimetic did not demonstrate toxicity or mutagenicity in various experiments, including bacterial mutation tests and animal experiments. Therefore, the substance exhibits good tolerance in animals at recommended doses, supporting its potential as a safe dietary supplement.

References:

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[2]. Kei Obayashi, et al. L-Ergothioneine scavenges superoxide and singlet oxygen and suppresses TNF-alpha and MMP-1 expression in UV-irradiated human dermal fibroblasts. DOI:10.1111/J.0142-5463.2005.00265_2.X

[3]. K. Dong, et al. A comparison of the relative antioxidant potency of L‐ergothioneine and idebenone. DOI:10.1111/j.1473-2165.2007.00330.x

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