Diosbulbin B (DIOB), a furanoid, is a major constituent of herbal medicine 
Dioscorea bulbifera L. Exposure to DIOB caused liver injury in humans and 
experimental animals. The mechanisms of DIOB-induced hepatotoxicities remain 
unknown. The present study demonstrated that DIOB induced hepatotoxicities in a 
time- and dose-dependent manner in mice. H&E stained histopathologic image 
showed the occurrence of necrosis in the liver obtained from the mice treated 
with DIOB at dose of 200 mg/kg. Pretreatment with KTC protected the animals from 
hepatotoxicities and hepatic GSH depletion induced by DIOB, increased area under 
the concentration-time curve of blood DIOB, decreased urinary excretion of GSH 
conjugates derived from DIOB, and increased urinary excretion of parent drug. 
Pretreatment with BSO exacerbated DIOB-induced hepatotoxicities. In order to 
define the role of furan moiety in DIOB-induced liver toxicities, we replaced 
the furan of DIOB with a tetrahydrofuran group by chemical hydrogenation of the 
furan ring of DIOB. No liver injury was observed in the animals given the same 
doses of tetrahydro-DIOB. The furan moiety was essential for DIOB-induced 
hepatotoxicities. The results implicate the cis-enedial reactive metabolite of 
DIOB was responsible for the observed toxicities. The observed modest depletion 
of hepatic GSH in DIOB-treated animals suggests the actions of one or more 
reactive metabolites, and the hepatic injury observed could be due at least in 
part to reactions of these metabolites with crucial biomolecules. Cytochrome 
P450 3A enzymes are implicated in DIOB-induced hepatotoxicities by catalyzing 
the formation of the reactive metabolite of DIOB.