A previous study has shown that Euonymus alatus (EA) has an antidotic activities against inflammation, suggesting possibility that EA can exert this beneficial effects to liver injury by an initial protection against drug-induced hepatocyte demage. The present study was undertaken to evaluate the protective effect of EA-extract on exprimentally induced hepatitis in ICR mice and to investigate some mechanisms responsible for its action.

Water EA extract was used in this experiments. The mice received i.p. a dose of 700 mg/kg galactosamine (GalN) together with 5 µg/kg of endotoxin (lps), or received i.v. 12mg/kg of concanavalin A (Con A). EA (4mg/mouse) was administrated on day -2, -1 and 0 before induction of liver injury. Liver injury was assessed by measurement of serum alanin amino-transferase (SGPT) levels on 9 hr after GaIN.LPS, or 8 hr after con A administration.

Treatment with either GaIN or LPS alone did not cause hepatitis. However, simultaneous administration of GaIN and LPS to mice resulted in LPS-dose dependent fulminant hepatitis. GaLN/LPS-induced liver injury was reduced when mice were given EA for 3 days before induction. This preventive effect of Ea was more prominent when EA was given by intraperitoneal route rather then by oral route. Pretriatmint of EA or dexamethasone infibited significantly TNFα production in GaIL/LPS-injured mice. However, EA-treatment did not influence TNFα-induced hepatitis in GaIN-sensitized mice, suggesting that TNFα is likly to act as one of final mediators of endotoxin action and the protective effect of EA might be manifested chiefly by inhibition of endotoxin-induced TNFα production, not by blocking the TNFα-action. Injection of Con A into mice evoked remarkable liver injury in a dose dependent fashion. This liver damage was reduced by EA-pretreatment. Dexamethasone significantly reduced both GaIL/LPS-induced and Con A-induced licer damages, showing synergism with EA. However, indomethacin reduced only GaIN/LPS-induced hepatitis, not for Con A-induced hepatitis.

these results led to the conclusion that EA may be able to contribute at least in part to prevent the drug-induced hepatotoxicity, and that its anti-hepatitis effects might be manifested directly by modulation of endogenous mediators, such as leukotriese D4, TNFα and free radical, and indirectly by regulation of immune mediated responses. Also these results suggested that EA could be developed as a potential antidotic agent.