title: Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats.
abstract: This study examined the effect of genistein isolated from Hydrocotyle sibthorpioides on chronic alcohol-induced hepatic injury and fibrosis. Rats underwent intragastric administration of alcohol (5.0-9.5g/kg) once a day for 24 weeks. A subset of rats were also intragastrically treated with genistein (0.5, 1 or 2mg/kg) once a day. Genistein significantly decreased the plasma alcohol concentration, inhibited the activities of alanine and aspartate aminotransferases and decreased levels of inflammatory mediators, including interleukin 6, tumor necrosis factor-α and myeloperoxidase, via down-regulation of nuclear factor-κB. Moreover, genistein effectively inhibited collagen deposition and reduced pathological tissue damage as determined by hepatic fibrosis biomarkers, such as total hyaluronic acid, laminin, and type III collagen. Mechanistically, studies showed that genistein markedly reduced lipid peroxidation, recruited the anti-oxidative defense system, inhibited CYP2El activity, promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-2, induced HSC apoptosis by down-regulating B-cell lymphoma 2 mRNA, and inhibited the expression of α-smooth muscle actin and transforming growth factor β(1) proteins. In conclusion, genistein exerts a preventative effect to ameliorate developing liver injury and even liver fibrosis induced by chronic alcohol administration in rats.
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D028041:Centella / Q000737:chemistry; D024061:Collagen Type III / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood; D019833:Genistein / Q000302:isolation & purification / Q000494:pharmacology*; D006651:Histocytochemistry; D006820:Hyaluronic Acid / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
chemical_list: D024061:Collagen Type III; D016207:Cytokines; D007797:Laminin; D016328:NF-kappa B; D000431:Ethanol; D006820:Hyaluronic Acid; D019833:Genistein; D019392:Cytochrome P-450 CYP2E1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase