[#2010-21] Shiitake Itoh, Ayano et al. Hepatoprotective Effect of Syringic Acid and Vanillic Acid on CC14 ­Induced Liver Injury

Hepatoprotective Effect of Syringic Acid and Vanillic Acid on CC1­Induced Liver Injury

Ayano ITOH, a  Katsuhiro ISODA, a  Masuo KONDOH, a  Malaya KAWASE, a  Akihiro WATARI, a Masakazu KOBAYASHI,b Makoto TAMESADA,b and Kiyohito YAGI * ‘a

a Graduate School of Pharmaceutical Sciences, Osaka University; 1-6 Yamada-oka, Saha, Osaka 565-0871, Japan: and b Research and Development Center, Kobayashi Pharmaceutical Co., Ltd.; 1-30-3 Toyokawa, Ibaraki, Osaka 567-0057, Japan. Received December 22, 2009; accepted March 16, 2010; published online March 19, 2010

The mycelia of the edible mushroom Lentinula edodes ( shiitake ) can be cultured in solid medium containing lignin, and the hot-water extracts (L.E.M.) is commercially available as a nutritional supplement. During the cultiva­tion, phenolic compounds, such as syringic acid and vanillic acid, were produced by lignin-degrading peroxidase secreted from L. edodes mycelia. Since these compounds have radical scavenging activity, we examined their pro­tective effect on oxidative stress in mice with CCI4-induced liver injury. We examined the hepatoprotective effect of syringic acid and vanillic acid on CCI4-induced chronic liver injury in mice. The injection of CCI4 into the peritoneal cavity caused an increase in the serum aspartate aminotransferase (AST) and alanine aminotrans­ferase (ALT) levels. The intravenous administration of syringic acid and vanillic acid significantly decreased the levels of the transaminases. Four weeks of CCI4 treatment caused a sufficiently excessive deposition of collagen fibrils. An examination of Azan-stained liver sections revealed that syringic acid and vanillic acid obviously sup­pressed collagen accumulation and significantly decreased the hepatic hydroxyproline content, which is the quan­titative marker of fibrosis. Both of these compounds inhibited the activation of cultured hepatic stellate cells, which play a central role in liver fibrogenesis, and maintained hepatocyte viability. These data suggest that the administration of syringic acid and vanillic acid could suppress hepatic fibrosis in chronic liver injury.