title: Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms.
abstract: Genistein is a naturally occurring plant-derived phytoestrogen present in the human diet, and is known to possess anti-cancer, anti-oxidant and anti-osteoporosis effects. Anti-inflammatory activity of genistein has been revealed in animal studies. In this paper, we investigated the anti-inflammatory effect of genistein on non-alcoholic steatohepatitis (NASH) rats induced by high fat diet (HFD), and explored its potential mechanisms. Rats were fed with normal chow diet or HFD for 12 weeks with or without low (4 mg/kg/day body weight) or high (8 mg/kg/day body weight) dose of genistein. Serum levels of aminotransferases, thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor beta (TGF-β(1)) were measured, hepatic inflammation, liver TBARS, IL-6, TNF-α and TGF-β(1) levels were determined, and proteins involved in mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways were assayed. The results showed that the NASH model rats reproduced typical pathogenetic and histopathological features of NASH in human, and genistein administration improved liver function, slowed down NASH progression, decreased the levels of TBARS, TNF-α and IL-6 in serum and liver, as well as inhibited IκB-α phosphorylation, nuclear translocation of NF-κB p65 subunit, and activation of c-Jun N-terminal kinase (JNK). In conclusion, genistein may be a promising drug to inhibit the inflammatory process and prevent liver damage in patients with NASH.
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Ji
authors.forename: Qinhe
authors.initials: Q
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Hao
authors.forename: Lina
authors.initials: L
authors.lastname: Guo
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Jianping
authors.initials: J
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Leng
authors.forename: Zhuoqin
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D018450:Disease Progression; D004789:Enzyme Activation / Q000187:drug effects; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D019833:Genistein / Q000008:administration & dosage*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000637:Transaminases / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004041:Dietary Fats; D016328:NF-kappa B; D017392:Thiobarbituric Acid Reactive Substances; D019833:Genistein; D000637:Transaminases; D048031:JNK Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases