L-Ergothioneine
[CAS# 497-30-3]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism
• Name: L-Ergothioneine
• Synonyms: NSC 7175; Phytothioneine; Sympectothion; Thiasine; Thioneine; Thiotane; thiotaine; (S)-; 2-Mercapto-N,N-dimethylhistidine methyl ester betaine; 2-Mercaptohistidine betaine; 2-Mercaptohistidine trimethylbetaine
• Molecular Formula: C₉H₁₅N₃O₂S
• Molecular Weight: 229.30
• CAS Registry Number: 497-30-3
• EC Number: 207-843-5
• SMILES: C[N+](C)(C)[C@@H](CC1=CNC(=S)N1)C(=O)[O-]

Properties

• Solubility: 1e+006 mg/L (25 °C water)
• Melting point: 246.79 °C
• Boiling Point: 573.21 °C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

L-Ergothioneine (ET) is a naturally occurring amino acid derivative first discovered in 1909 by French chemist Joseph Louis Gautier. It was isolated from ergot fungus, a parasitic fungus that grows on rye and other grains. Gautier originally named it "ergothioneine" because it was related to ergot, but it was later discovered to be present in a variety of other organisms, including plants, animals, and bacteria. L-ergothioneine, whose chemical structure was elucidated in the 1930s, is a thiohistidine derivative with a sulfur atom in position 2 of the imidazole ring. L-Ergothioneine is known for its powerful antioxidant properties. It acts as a scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS), protecting cells and tissues from oxidative damage caused by free radicals. The unique sulfur-histidine structure of L-ergothioneine enables it to effectively neutralize oxidative stress and mitigate the harmful effects of ROS on cellular components, including lipids, proteins, and DNA.

L-Ergothioneine also has anti-inflammatory properties. It modulates inflammatory pathways by inhibiting the production of proinflammatory cytokines and mediators, such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS). By reducing inflammation, ET helps reduce tissue damage, relieve pain, and promote tissue repair in a variety of inflammatory conditions. L-Ergothioneine plays an important role in skin health and protection against environmental stressors. It is actively transported into skin cells where it acts as a cellular antioxidant and UV protectant. ET helps counteract oxidative damage caused by UV rays, prevent DNA mutations, and maintain skin integrity, thereby reducing the risk of photoaging, sunburn, and skin cancer. Emerging research suggests that L-ergothioneine may exert neuroprotective effects and contribute to brain health. ET readily crosses the blood-brain barrier and accumulates in brain tissue, acting as a potent antioxidant and modulating neuroinflammatory pathways. L-Ergothioneine helps protect neuronal function, improve cognitive performance, and slow the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and stroke. Research suggests that L-ergothioneine may be cardioprotective and beneficial to cardiovascular health. ET scavenges free radicals in the cardiovascular system, alleviates endothelial dysfunction caused by oxidative stress, and enhances nitric oxide bioavailability, thereby improving vascular function and reducing the risk of atherosclerosis, hypertension, and cardiovascular events.

References

2024. Ergothioneine ameliorates metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) by enhancing autophagy, inhibiting oxidative damage and inflammation. Lipids in Health and Disease.
DOI: 10.1186/s12944-024-02382-9

2024. Engineering Saccharomyces cerevisiae for expressing l-ergothioneine as a probiotic supplement. Biotechnology Journal.
DOI: 10.1002/biot.202400527

1950. Synthesis of Ergothioneine. Nature.
DOI: 10.1038/166106a0