Abstract
Objective
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
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
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. 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
XJDHD inhibits TNF-α-induced apoptosis of hepatocytes by promoting the expression of nuclear factor κ B-regulated anti-apoptotic genes. Rehmannia glutinosa Libosch. is the effective herb of XJDHD and galactose is an active component in this protection.
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Supported by the National Natural Science Foundation of China (No. 81072766), Beijing Natural Science Foundation (No. 7112066), and 215 Program from Beijing Public Health Bureau (No. 2013-2-11)
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Liu, Ym., Zhu, LL., Li, R. et al. Xijiao Dihuang Decoction (犀角地黄汤) and Rehmannia glutinosa Libosch. protect mice against lipopolysaccharide and tumor necrosis factor alpha-induced acute liver failure. Chin. J. Integr. Med. 25, 446–453 (2019). https://doi.org/10.1007/s11655-015-2141-2
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DOI: https://doi.org/10.1007/s11655-015-2141-2