Genipin prevents fulminant hepatic failure resulting in reduction of lethality through the suppression of TNF-α production

Genipin is a metabolite derived from the herbal medicine Inchinko-to. Little is known about the mechanism of genipin action on acute liver injury through inflammatory cytokines. We examined the effects of genipin on production of TNF-α in vivo and in vitro. Mice were given GalN/LPS with or without genipin treatment. All mice not given genipin died within 12 h. But in mice given genipin, 8 of 15 mice survived for 24 h after GalN/LPS administration. Histologically, hepatic necrosis and inflammatory cells infiltration were significantly slight in mice given genipin. Serum AST and ALT activity were significantly lower in mice given genipin. Serum and liver homogenate TNF-α levels were significantly lower in mice given genipin. However, in IL-6 and IL-1β, there were no significant differences in mice given and not given genipin. TNF-α, NF-κB activation and TNF-α mRNA expression in a cultured mouse macrophage-like cell line J774.1 were significantly suppressed by genipin administration. In conclusion, the present findings suggest that genipin, a metabolite derived form the herbal medicine Inchinko-to improved acute liver dysfunction by suppressive effect of TNF-α production.