Protective effects of Asiaticoside on acute liver injury induced by lipopolysaccharide/D-galactosamine in mice

Zhang, Li; Li, Hong-zhong; Gong, Xia; Luo, Fu-ling; Wang, Bin; Hu, Ning; Wang, Chang-dong; Zhang, Zhuo; Wan, Jing-yuan

doi:10.1016/j.phymed.2010.01.008

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Volume 17, Issue 10 , Pages 811-819, August 2010

Protective effects of Asiaticoside on acute liver injury induced by lipopolysaccharide/D-galactosamine in mice

Li Zhang
- Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
- Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
- Contributed equally to this work.
Hong-zhong Li
- Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
- Pharmacological and Toxicological Evaluation Center, Chongqing Pharmaceutical Research Institute, Chongqing 400061, People’s Republic of China
- Contributed equally to this work.
Xia Gong
- Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
- Department of Anatomy, Chongqing Medical University, Chongqing 400016, People’s Republic of China
Fu-ling Luo
- Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
- Department of Pharmacy, The first Afﬁliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China
Bin Wang
- Department of Anesthesiology, The first Afﬁliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China
Ning Hu
- Department of Orthopedics, The first Afﬁliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China
Chang-dong Wang
- Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
Zhuo Zhang
- Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
Jing-yuan Wan
- Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
- Corresponding author: Tel.: +8602368485038; fax: +8602386134172.

published online 22 February 2010.

Abstract

Asiaticoside (AS), a triterpenoid product isolated from Centella asiatica, has been described to exhibit anti-inﬂammatory 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-α) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic tissue TNF-α 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-α mRNA expression in liver tissues and plasma TNF-α. 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-α and MAPKs.

Keywords: Asiaticoside, Acute liver injury, Lipopolysaccharide, D-galactosamine, Mitogen-activated protein kinases