Ergothioneine (EGT) is a sulfur‐containing amino acid, and is presumed to function as a natural antioxidant. The purpose of this study was to identify the nature of the antioxidant activity and investigate the effects of EGT on UV‐induced cellular response. In chemical studies, EGT scavenged the superoxide anion radical (•O2–) and singlet oxygen (1O2). In cultured fibroblasts, EGT suppressed TNF‐α upregulation by UVB irradiation. In addition, in fibroblasts exposed to UV‐A, EGT suppressed the expression of matrix metalloproteinase 1 (MMP‐1) protein by nearly 50% and reduced MMP‐1 mRNA expression. From these results, we conclude that EGT scavenges reactive oxygen species generated by both type I and type II photosensitization and suppresses both TNF‐α expression and MMP‐1 at their transcriptional level. EGT may reduce skin anti‐aging effects after UV irradiation by the scavenging of •O2– and 1O2, and reducing signals for protease and inflammatory activity.
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