Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of
bile acids in body and liver. Proper regulation of
bile acids in liver cells is critical for liver injury. We previously reported the effects of
dioscin against α-naphthylisothio-
cyanate (ANIT)-induced
cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and
dioscin was used for the treatment. The results showed that
dioscin markedly altered relative liver weights, restored ALT, AST, ALP, TBIL, GSH, GSH-Px, MDA, SOD levels, and rehabilitated ROS level and cell apoptosis. In mechanism study,
dioscin not only significantly regulated the
protein levels of Ntcp, OAT1, OCT1, Bsep and Mrp2 to accelerate
bile acids excretion, but also regulated the expression levels of Bak, Bcl-xl, Bcl-2, Bax,
Caspase 3 and
Caspase 9 in vivo and in vitro to improve apoptosis. In addition,
dioscin markedly inhibited PI3K/Akt pathway and up-regulated the levels of Nrf2, GCLc, GCLm, NQO1 and HO-1 against oxidative stress (OS) caused by
bile acids. These results were further validated by inhibition of PI3K and Akt using the inhibitors of
wortmannin and
perifosine in SCHs. Our data showed that
dioscin had good action against ANIT-caused
intrahepatic cholestasis through regulating transporters, apoptosis and OS. This natural product can be considered as one active compound to treat
intrahepatic cholestasis in the future.