Abstract
Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4-) induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg) reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB) p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine Transaminase / blood
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Animals
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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Aspartate Aminotransferases / blood
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Biphenyl Compounds / chemistry
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Carbon Tetrachloride
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Catechin / analogs & derivatives*
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Catechin / pharmacology
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Catechin / therapeutic use
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cyclooxygenase 2 / metabolism
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Enzyme Activation / drug effects
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Ferrous Compounds / toxicity
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Gene Expression Regulation / drug effects
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Hep G2 Cells
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Humans
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Hydrogen Peroxide / toxicity
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Lipid Peroxidation / drug effects
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Liver / drug effects
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Liver / pathology
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Liver Diseases / blood
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Liver Diseases / drug therapy*
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Liver Diseases / enzymology
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Liver Diseases / genetics
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MAP Kinase Signaling System / drug effects*
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Malondialdehyde / metabolism
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NF-kappa B / metabolism*
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Phenols / pharmacology
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Phenols / therapeutic use*
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Picrates / chemistry
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Protein Transport / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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Rats, Sprague-Dawley
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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tert-Butylhydroperoxide
Substances
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Antioxidants
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Biphenyl Compounds
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Ferrous Compounds
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Interleukin-1beta
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NF-kappa B
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Phenols
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Picrates
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Tumor Necrosis Factor-alpha
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oligonol
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ferrous sulfate
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Malondialdehyde
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Catechin
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tert-Butylhydroperoxide
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Hydrogen Peroxide
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Carbon Tetrachloride
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1,1-diphenyl-2-picrylhydrazyl
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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PTGS2 protein, human
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Aspartate Aminotransferases
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Alanine Transaminase
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Proto-Oncogene Proteins c-akt