Explore the detailed analysis of ergothioneine, a powerful antioxidant known for its skin protective, anti-aging, and inflammation-resistant properties.

Ergothioneine, known as the antioxidant queen among the cosmetics elite, Estée Lauder’s signature treasure, the strongest antioxidant on Earth, the guardian of cells, and the formidable “overlord of antioxidants” – these are just a few of the titles bestowed upon ergothioneine!

As a natural antioxidant, ergothioneine protects proteins in DNA from oxidative damage. As a rare sulfur-containing amino acid, it naturally exists in the human body as a cellular protector and antioxidant, with properties that fight photoaging, oxidation, and inflammation.

What is Ergothioneine?

Origin:
Ergothioneine is a rare natural amino acid derivative. In 1909, Charles Tanret isolated a unique crystalline sulfur-containing compound while researching ergot fungi that spoil rye grains. He named this water-soluble thiol after the ergot fungus.

It is a homologous component in the human body, accumulating at high concentrations in various cells and tissues, most abundantly in red blood cells, bone marrow, liver, kidneys, and the lenses and corneas of the eyes.

However, our bodies cannot synthesize ergothioneine; it must be obtained externally, with mushrooms containing the highest purity of ergothioneine. Compared to traditional antioxidants like vitamin C and glutathione, ergothioneine is safer, milder, more stable, and has stronger antioxidant capabilities.

Mechanism of Free Radical Scavenging:

About 90% of the oxygen we breathe is used by mitochondria to generate cellular energy – Adenosine Triphosphate (ATP), while 0.2-2% of the oxygen produces reactive oxygen species (ROS), highly chemically active free radicals. The most unstable and damaging ROS are the peroxyl radical (•O2−) and hydroxyl radical (•OH), which directly cause inflammation, aging, and death of lipids, proteins, polysaccharides, and DNA in the skin.

Ergothioneine EGT is valued in the industry because it is currently the only component that can actively cross cell membranes, enter cells, and neutralize peroxyl and hydroxyl radicals without disrupting the body’s natural antioxidant defense system.

Mechanism of Action:

The transport and function of ergothioneine in biological systems depend on a special transport protein, OCTN1 (Organic Cation Transporter N1, produced by the SLC22A4 gene). OCTN1, found in keratinocytes and melanocytes, has a high affinity for ergothioneine, making it easily accepted, absorbed, and utilized by skin tissues and cells.

Through OCTN1 present in cell and mitochondrial membranes, ergothioneine is transported to mitochondria, the primary site of free radical production, protecting mitochondria from oxidative damage while directly eliminating reactive oxygen species to ultimately delay cellular aging.

Antioxidant Protection of Mitochondria:

1. The main energy source of human cells, ATP, is generated in mitochondria through the conversion of fatty acids, inevitably leading to the production of free radicals.
2. As a supreme antioxidant, ergothioneine is the only antioxidant with a clear mechanism that can repair mitochondria.

Protective Effects on Fibroblasts:

Fibroblasts are the most common cells in connective tissue, actively involved in secreting structural proteins that make up the extracellular matrix, closely linked to the aging process of the skin. Ergothioneine protects fibroblasts by reducing the degradation of matrix metalloproteinase-1 (MMP-1), increasing the production of type I collagen, enhancing their survival capabilities, inhibiting the production of reactive oxygen species induced by UVA, activating transcription factor AP-1, and upregulating the nuclear translocation of the Nrf2 factor (a basic leucine zipper protein that acts as a conductor of oxidation and electrophilic stress responses, stabilizing the genome) through the Nrf2 pathway, inducing the expression of antioxidant genes and the production of glutathione in fibroblasts after UVA exposure.

Glutathione, a rich non-protein thiol in cells, acts as an antioxidant to protect cells from damage by reactive oxygen species. The impact of ergothioneine on glutathione levels in fibroblasts signifies its potency not only as an effective antioxidant but also as a strong antioxidant inducer.

Anti-inflammatory and Other Chronic Diseases:

Ergothioneine has been proven to inhibit the activation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and the upregulation of TNF-α (tumor necrosis factor-alpha) induced by UVB exposure; it prevents the activation and increase of inflammatory cytokines IL-8 (interleukin-8) and IL-6 (interleukin-6) mediated by TN

F-α in epithelial cells; and by activating the p38 and JNK signaling pathways, it prevents cell death caused by free fatty acids, thereby providing resistance to inflammation and even chronic diseases.

Skin Anti-glycation Effects:

Protein glycation, a common phenomenon during skin aging, alters the physicochemical properties of collagen, increasing the content of glycation products in the skin, leading to tissue stiffness and accelerated skin aging. Studies have found that using ergothioneine and its derivatives in cosmetics, such as gel solutions, toners, and lotions, with ergothioneine content between 0.001-10%, effectively reduces collagen glycation, helping to prevent and treat glycation-related skin tension loss and signs of aging (EP1166768A1).

Photodamage Protection:

Ergothioneine improves cellular hypoxia states after exposure to ultraviolet and blue light, helping cells restore normal metabolic functions, effectively blocking skin damage from ultraviolet and blue light, and promoting skin repair after photodamage.

Whitening and Inhibition of Melanin Production:

Research has proven that ergothioneine’s inhibition of tyrosinase is superior to common inhibitors, blocking pigment formation and deposition, brightening skin tone, and whitening skin.

After 48 hours of positive control with kojic acid treatment, melanin production in cells was reduced, with melanin content reaching 82.01% of the blank control group. When the concentration of ergothioneine was 0.25 mg/mL, the melanin content in cells was 58.87%, already better than the 25 μg/mL kojic acid whitening effect.

Comparison with Other Antioxidants:

In 2007, Estée Lauder pitted ergothioneine against Elizabeth Arden’s star ingredient, idebenone, in a study published in the Journal of Cosmetic Dermatology, comparing ergothioneine with another antioxidant component, idebenone. The results showed that in eliminating free radicals and protecting cells from ultraviolet-induced reactive oxygen, ergothioneine was stronger than coenzyme Q10 and idebenone.

To determine the direct elimination capabilities of ergothioneine and idebenone quinone against hydrogen peroxide, researchers added dihydrorhodamine, hydrogen peroxide, and either ergothioneine or idebenone quinone to the culture medium. They measured the fluorescence intensity over 120 minutes to verify the hydrogen peroxide scavenging ability of ergothioneine and idebenone quinone. The experiment showed that ergothioneine’s scavenging ability was more effective at all testing time points compared to idebenone quinone.

In addition to hydrogen peroxide, researchers also used simulated ultraviolet light (UVA340) exposure on fibroblast samples treated with ergothioneine or idebenone quinone. One hour later, idebenone quinone reduced the reactive oxygen in fibroblasts by 6.2%, while ergothioneine reduced it by 17.5%.

Comparison with Coenzyme Q10:

In experiments, researchers used thymidine-induced lipid peroxidation in liposomes as an indicator. Lipid peroxidation levels were reduced by 67% with 4.6μg/mL ergothioneine treatment, while only 37% reduction was observed with 4.6μg/mL coenzyme Q10 treatment.

references:

Qin Cheng. BV2 cell model to study the function of OCTN1 transporter and its mechanism of mediating anti-inflammatory/antioxidative effects [D]. Huazhong University of Science and Technology, 2021. DOI: 10.27157/d.cnki.ghzku.2021.004888.

Zhang Mengmeng, Zhang Qian, Zhang Guochen. Functions of ergothioneine amino acids in Enoki mushroom extract and its application prospects in the food industry [J]. Anhui Agricultural Sciences, 2014(11):3385-3387.

Weng Yayun, et al. Construction and application of cell models stably expressing human OCTN1/OCTN2 [J]. Acta Pharmaceutical Sinica, 2016, 51(06).

Pan Hongyu, Guo Liqiong, Lin Junfang. Research progress on the distribution and metabolism of ergothioneine in the body and its role in diseases[J]. Food Science.

Liu Xinqi. Efficacy evaluation of ergothioneine and development and application of raw materials. Master’s thesis of Shanghai University of Technology. 2020.

Wang Yan, Li Yahuan, Mo Yuli, Hu Jingjing, Zhang Yixin, Wang Jie. In vitro antioxidant capacity of Pleurotus eryngii ergothioneine (EGT) and the influence of environmental factors on its stability [J]. Food and Fermentation Industry, 2019, 45(14):47-56.

Markova N G , Karaman-Jurukovska N , Dong K K ,et al. Skin cells and tissue are capable of using l-ergothioneine as anintegral component of their antioxidant defense system[J]. free radic biol med,2009, 46(8):1168-1176.

Dermato-protective properties of ergothioneine through induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated Human keratinocytes.

[12] Liao, Wayne C., et al. “Kinetics of ergothioneine inhibition of mushroom tyrosinase.” Applied biochemistry and biotechnology 166 (2012): 259-267.

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