| DOI | Resolve DOI: https://doi.org/10.1016/j.lfs.2003.10.021 |
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| Author | Search for: Banskota, Arjun H.; Search for: Nguyen, Nhan Trung; Search for: Tezuka, Yasuhiro; Search for: Le Tran, Quan; Search for: Nobukawa, Takahiro; Search for: Kurashige, Youichi; Search for: Sasahara, Masakiyo; Search for: Kadota, Shigetoshi |
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| Format | Text, Article |
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| Subject | Secoisolariciresinol; Isotaxiresinol; Apoptosis; Taxus yunnanensis; Hepatoprotective effect; TNF-α; D-Galactosamine; Lipopolysaccharide; Lignan |
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| Abstract | effects of secoisolariciresinol (1) and isotaxiresinol (2), two major lignans isolated from the wood of Taxus yunnanensis, on tumor necrosis factor-α (TNF-α)-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 μg/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-α and interferon-γ (IFN-γ) 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-α and IFN-γ levels. In a separate experiment, both lignans had a significant dose-dependent protective effect on d-GalN/TNF-α-induced cell death in primary cultured mouse hepatocytes and TNF-α-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-α and IFN-γ production by activated macrophages and direct inhibition of the apoptosis induced by TNF-α. |
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| Publication date | 2004-03-18 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NRC publication | This is a non-NRC publication"Non-NRC publications" are publications authored by NRC employees prior to their employment by NRC. |
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| NPARC number | 21274279 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | cbdce5f1-6757-45f0-8885-e14d44d6e7df |
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| Record created | 2015-03-09 |
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| Record modified | 2020-04-17 |
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