| RRC ID |
42121
|
| Author |
Banskota AH, Nguyen NT, Tezuka Y, Le Tran Q, Nobukawa T, Kurashige Y, Sasahara M, Kadota S.
|
| Title |
Secoisolariciresinol and isotaxiresinol inhibit tumor necrosis factor-alpha-dependent hepatic apoptosis in mice.
|
| Journal |
Life Sci
|
| Abstract |
The effects of secoisolariciresinol (1) and isotaxiresinol (2), two major lignans isolated from the wood of Taxus yunnanensis, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (d-GalN)/lipopolysaccharide (LPS) were investigated in mice. Co-administration of d-GalN (700 mg/kg) and LPS (10 microg/kg) resulted in a typical hepatic apoptosis characterized by DNA fragmentation and the formation of apoptotic bodies. Serum glutamic pyruvic transaminase (sGPT) and glutamic oxaloacetic transaminase (sGOT) levels were also raised at 8 h after d-GalN/LPS intoxication due to a severe necrosis of hepatocytes. Pre-administration of 1 or 2 (50, 10 mg/kg, i.p.) 12 and 1 h before d-GalN/LPS significantly reduced DNA fragmentation and prevented chromatin condensation, apoptotic body formation and hepatitis. Pro-inflammatory cytokines such as TNF-alpha and interferon-gamma (IFN-gamma) secreted from LPS-activated macrophages are important mediators of hepatocyte apoptosis in this model. Pre-treatment with 1 or 2 significantly inhibited the elevation of serum TNF-alpha and IFN-gamma levels. In a separate experiment, both lignans had a significant dose-dependent protective effect on d-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes and TNF-alpha-mediated cell death in murine L929 fibrosarcoma cells. These results indicated that 1 and 2 prevent d-GalN/LPS-induced hepatic injury by inhibiting hepatocyte apoptosis through the blocking of TNF-alpha and IFN-gamma production by activated macrophages and direct inhibition of the apoptosis induced by TNF-alpha.
|
| Volume |
74(22)
|
| Pages |
2781-92
|
| Published |
2004-4-16
|
| DOI |
10.1016/j.lfs.2003.10.021
|
| PII |
S0024320504000906
|
| PMID |
15043992
|
| MeSH |
Alanine Transaminase / blood
Animals
Apoptosis / drug effects*
Aspartate Aminotransferases / blood
Butylene Glycols / administration & dosage
Butylene Glycols / pharmacology*
Butylene Glycols / therapeutic use
Chemical and Drug Induced Liver Injury / blood
Chemical and Drug Induced Liver Injury / etiology
Chemical and Drug Induced Liver Injury / prevention & control*
Dose-Response Relationship, Drug
Drug Therapy, Combination
Furans / administration & dosage
Furans / pharmacology*
Furans / therapeutic use
Galactosamine / pharmacology
Injections, Intraperitoneal
Interferon-gamma / blood
Lignans*
Lipopolysaccharides / pharmacology
Liver / drug effects
Liver / metabolism
Liver / pathology
Male
Mice
Mice, Inbred Strains
Phytotherapy
Plant Extracts / administration & dosage
Plant Extracts / pharmacology*
Plant Extracts / therapeutic use
Plants, Medicinal
Taxus
Tumor Necrosis Factor-alpha* / analysis
Tumor Necrosis Factor-alpha* / metabolism
|
| IF |
3.647
|
| Times Cited |
7
|
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
PHARMACOLOGY & PHARMACY
|
| Resource |
| Human and Animal Cells |
L929 |
