Objective:

2

To investigate the hepatoprotective effect of Xijiao Dihuang Decoction (犀角地黄汤

XJDHD) on lipopolysaccharide (LPS)- and tumor necrosis factor alpha (TNF-α)-induced acute liver failure (ALF) as well as the underlying mechanism of action

and to clarify the key herbs and components of XJDHD.

Methods:

2

LPS/D-galactosamine (D-GalN) or TNF-α/D-GalN were intraperitoneally injected into C57BL/6J mice to induce ALF. Simultaneously

XJDHD or its individual herbs and components were orally administered. Survival rates

transaminase levels in serum

and hepatic histology were examined to evaluate the effects of XJDHD. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and real-time polymerase chain reaction were additionally performed to expound the mechanism underlying the anti-apoptotic activity of XJDHD.

Results:

2

Oral administration of XJDHD protected mice from lethal liver failure induced by LPS and TNF-α

with notable amelioration of liver injury in histology and a significant decrease in transaminase levels in serum. XJDHD significantly inhibited apoptosis of hepatocytes and enhanced expression of the antiapoptosis genes

c-Flip

Iap1

Gadd45b and A20 (all

P

<

0.05). In addition

Rehmannia glutinosa

Libosch. was identified as the key herb of XJDHD and galactose as the effective component of

Rehmannia glutinosa

Libosch. that protects against ALF.

Conclusions:

2

XJDHD inhibits TNF-α-induced apoptosis of hepatocytes by promoting the expression of nuclear factor κB-regulated anti-apoptotic genes.

Rehmannia glutinosa

Libosch. may be the most effective herb of XJDHD and galactose is an active component in this protection.