Protective effects of Asiaticoside on acute liver injury induced by lipopolysaccharide/D-galactosamine in mice.
Asiaticoside (AS), a triterpenoid product isolated from Centella asiatica, has been described to exhibit anti-in fl ammatory activities in several inflammatory models. However, the effects of AS on liver injury are poorly understood. The present study was undertaken to investigate whether AS is efficacious against Lipopolysaccharide (LPS) /D-galactosamine (D-GalN)-induced acute liver injury in mice and its potential mechanisms. AS (5, 10 and 20 mg/kg/d) was pretreated orally once daily for 3 days before LPS/D-GalN injected in mice. The mortality, hepatic tissue histology, plasma levels of Tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic tissue TNF-alpha and caspase-3 activity were measured. Besides, western blotting analysis of phospho-p38 mitogen-activated protein kinase (phospho-p38 MAPK), phospho-c-jun N-terminal kinase (phospho-JNK) and phospho-extracellular signal regulated kinase (phospho-ERK) were determined. As a result, AS showed significant protection as evidenced by the decrease of elevated aminotransferases, hepatocytes apoptosis and caspase-3, alleviation of mortality and improvement of liver pathological injury in a dose-dependent manner. Further, we found that AS dose-dependently reduced the elevation of phospho-p38 MAPK, phospho-JNK, phospho-ERK protein and TNF-alpha mRNA expression in liver tissues and plasma TNF-alpha. These results suggest that AS has remarkable hepatoprotective effects on LPS/D-GalN-induced liver injury and the possible mechanism is related to inhibition of TNF-alpha and MAPKs.
Zhang
Li
L
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Li
Hong-Zhong
HZ
Gong
Xia
X
Luo
Fu-Ling
FL
Wang
Bin
B
Hu
Ning
N
Wang
Chang-Dong
CD
Zhang
Zhuo
Z
Wan
Jing-Yuan
JY
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D017931:DNA Primers; D005688:Galactosamine / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D014315:Triterpenes / Q000494:pharmacology*
D017931:DNA Primers; D008070:Lipopolysaccharides; D014315:Triterpenes; D005688:Galactosamine; C004446:asiaticoside