title: Oligonol Ameliorates CCl₄-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways.
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.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jeonghyeon
authors.initials: J
authors.lastname: Bak
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Nam Kyung
authors.initials: NK
authors.lastname: Je
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.affiliation: Graduate School of Science and Engineering for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Yokozawa
authors.affiliation: Department of Anatomy, College of Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jeon-Ok
authors.initials: JO
authors.lastname: Moon
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001713:Biphenyl Compounds / Q000737:chemistry; D002251:Carbon Tetrachloride; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005296:Ferrous Compounds / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use*; D010851:Picrates / Q000737:chemistry; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D020122:tert-Butylhydroperoxide
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D005296:Ferrous Compounds; D053583:Interleukin-1beta; D016328:NF-kappa B; D010636:Phenols; D010851:Picrates; D014409:Tumor Necrosis Factor-alpha; C514283:oligonol; C020748:ferrous sulfate; D008315:Malondialdehyde; D002392:Catechin; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D002251:Carbon Tetrachloride; C004931:1,1-diphenyl-2-picrylhydrazyl; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt