Hepatoprotective effects of irisolidone on tert-butyl hyperoxide-induced liver injury

To clarify the hepatoprotective effects of kakkalide and its metabolite irisolidone by human fecal microflora, their effects on tert-butyl hydroperoxide (t-BHP)-injured HepG2 cells and mice were investigated. Irisolidone protected HepG2 cells against cytotoxicity induced by t-BHP. However, kakkalide did not protect cytotoxicity. When kakkalide 100 mg/kg was orally administered to mice injured by t-BHP, it significantly inhibited the increase in plasma alanine aminotransferase and aspartate aminotransferase activities by 84% and 85% of t-BHP-treated control group, respectively. The inhibitory effect of kakkalide is much more potent than that of silybin, a hepatoprotective agent. However, intraperitoneally administered kakkalide did not exhibit hepatoprotective activity. When irisolidone was intraperitoneally administered to mice, it exhibited potent hepatoprotective activity. Based on these findings, irisolidone can be hepatoprotective and kakkalide may be a prodrug transformed to irisolidone.