Many physiologically active hepatoprotective substances, such as those with antifibrotic activity, have been found in tea, fruits, and vegetables.1,2) The edible mushroom Lentinula edodes (shiitake) contains several bioactive compounds, including compounds with immunoprotective and antiatherogenic activities and one compound with an anti-human immunodeficiency virus (HIV) effect. [3][4][5] The mycelia of L. edodes can be cultured in solid medium, and the extract obtained by hot-water treatment (L.E.M.) is commercially available as a nutritional supplement. In our previous study, we found that L.E.M. exerts a hepatoprotective effect on dimethylnitrosamine (DMN)-induced liver fibrosis and Dgalactosamine-induced acute liver injury. 6,7) In the chronic liver injury model that uses DMN, the L.E.M. treatment suppressed the activation of hepatic stellate cells, which play a central role in liver fibrosis. The L.E.M. treatment also protected hepatocytes in the acute liver injury model that uses Dgalactosamine. We also found that the oral or intraperitoneal administration of L.E.M. suppressed immune-mediated liver injury. Therefore, L.E.M. is a promising plant extract for the prevention of liver failure. With the aim of developing effective drugs for liver diseases, we examined the protective effect of a single L.E.M. component against liver injury.The main components of L.E.M. are sugars, proteins, and polyphenolic compounds. The polyphenols act as antioxidants by scavenging reactive oxygen species (ROS), which produce oxidative stress and can adversely affect many cellular processes. Polyphenols have been proposed to protect against several diseases, including cancers, cardiovascular disease, and neurodegenerative disorders. [8][9][10] In our previous study, we found that the polyphenol-rich fraction of L.E.M. inhibits hepatic stellate cell activation, which is the
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