title: Hepatoprotective effects of zingerone on carbon tetrachloride- and dimethylnitrosamine-induced liver injuries in rats.
abstract: In this study, we investigated the hepatoprotective and anti-fibrotic effects of zingerone, one of the active components of ginger, against carbon tetrachloride (CCl4)- and dimethylnitrosamine (DMN)-induced liver injuries in rats, respectively. Oral administration of zingerone (10 mg/kg) reduced CCl4-induced abnormalities in liver histology, serum alanine aminotransferase and aspartate aminotransferase levels, and liver malondialdehyde levels. Zingerone treatment attenuated CCl4-induced increases in inflammatory mediators, including tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase mRNA levels. Western blot analysis showed that zingerone suppressed activation of nuclear factor-kappa B (NF-κB) p65 and phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinases (MAPKs). Liver fibrosis induced by DMN (10 mg/kg, intraperitoneally) was ameliorated by administration of zingerone (10 and 20 mg/kg, orally). Zingerone treatment reduced DMN-induced elevation of hydroxyproline content and hepatic stellate cell activation. In conclusion, zingerone 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 MAPKs. Moreover, zingerone had hepatoprotective and anti-fibrotic effects against DMN-induced liver injury suggesting its usefulness in the prevention of liver inflammation and the development of hepatic fibrosis.
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea.
authors.forename: Kyoung Ook
authors.initials: KO
authors.lastname: Cheong
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea.|Hazard Substances Analysis Team, Center for Food and Drug Analysis, Busan Regional Food & Drug Administration, 65, 356-Gil, Shinseon-ro, Nam-gu, Busan, 47366, Korea.
authors.forename: Dong-Su
authors.initials: DS
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea.
authors.forename: Jeonghyeon
authors.initials: J
authors.lastname: Bak
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea.
authors.forename: Changyong
authors.initials: C
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea.
authors.forename: Kyung Wook
authors.initials: KW
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea.
authors.forename: Nam Kyung
authors.initials: NK
authors.lastname: Je
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.affiliation: Department of Anatomy College of Medicine, Pusan National University, Yangsan, 50612, Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 46241, Korea. mjo@pusan.ac.kr.
authors.forename: Jeon-Ok
authors.initials: JO
authors.lastname: Moon
mesh_terms: D000410:Alanine Transaminase; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D004128:Dimethylnitrosamine; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D018836:Inflammation Mediators; C013738:zingerone; D006139:Guaiacol; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020928:Mitogen-Activated Protein Kinases; D004128:Dimethylnitrosamine; D006909:Hydroxyproline
keywords: Anti-fibrotic effect; Antioxidant; Hepatoprotective effect; MAPKs; NF-κB; Zingerone