Mao (Ephedra sinica Stapf) protects against D-galactosamine and lipopolysaccharide-induced hepatic failure.
Mao is one component of various traditional herbal medicines. We examined the effects of Mao on an acute liver failure model treated with d-galactosamine (GalN) and lipopolysaccharide (LPS). The lethality of mice administrated Mao with GalN/LPS was significantly decreased compared with that in mice without Mao. Hepatic apoptosis and inflammatory cell infiltration were slight in Mao-treated mice. Serum alanine aminotransferase (ALT) and total bilirubin (T.Bil) activity, tumor necrosis factor alpha (TNF-alpha) levels and caspase 8, 9, and 3 activity in the liver were significantly lower in mice administrated Mao. But, Serum interleukin-6 (IL-6), IL-10 levels and signal transducers and activators of transcription 3 (STAT3) activity in the liver were significantly higher in mice administrated Mao. To investigate the effect of STAT3, we used AG490, which selectively inhibits the activation of Janus kinase (JAK) family tyrosine kinase and inhibits the constitutive activation of STAT3. There was significant aggravation in hepatic apoptosis treated with Mao and AG490 compared with Mao alone. In conclusions, Mao significantly suppressed hepatic apoptosis by inhibition of TNF-alpha production and caspase activity. Furthermore, it is also suggested that Mao, which activates STAT3 induced by IL-6, may be a useful therapeutic tool for fulminant hepatic failure.
Yamada
Ikuhiro
I
Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Goto
Takashi
T
Takeuchi
Satoko
S
Ohshima
Shigetoshi
S
Yoneyama
Kazuo
K
Shibuya
Tomomi
T
Kataoka
Ei
E
Segawa
Daisuke
D
Sato
Wataru
W
Dohmen
Takahiro
T
Anezaki
Yumiko
Y
Ishii
Hajime
H
Ohnishi
Hirohide
H
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000032:analysis; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D029790:Ephedra sinica / Q000737:chemistry*; D005688:Galactosamine / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D016207:Cytokines; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D005688:Galactosamine; D020169:Caspases