title: Oral administration of soy-derived genistin suppresses lipopolysaccharide-induced acute liver inflammation but does not induce thymic atrophy in the rat.
abstract: Genistein, the principal isoflavone present in soy, has been identified as a protein tyrosine kinase (PTK) inhibitor that has in vitro anti-inflammatory effects. Whether genistein has in vivo anti-inflammatory effects remains unknown yet. Injecting or feeding rats with the unconjugated form of genistein (aglycone) results in decreased thymic weight and lymphocytopenia. However, 95-99% of genistein is present as the conjugated form genistin (genistein glycoside) in soy or soy-derived products. This study was undertaken to reveal whether genistin, as well as genistein, has anti-inflammatory effects in vivo. After oral administration of equimolar genistein (namely 7.4 or 74 micromol/dose) at daily doses of 2.0 or 20 mg/kg, or genistin at daily doses of 3.2 or 32 mg/kg for 3 days to male rats, both aglycone and glycoside suppressed the production of lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 in both from the liver and in the sera. Aglycone induced thymic atrophy while glycoside did not. In vitro preincubation of liver slices from naïve rat with genistein aglycone or glycoside suppressed LPS-induced TNF-alpha production in a dose-dependent manner. Taken together, both in vivo and in vitro administration of genistin and genistein suppressed LPS-induced liver pro-inflammatory cytokine production. However, equimolar oral administration of genistin did not induce thymus atrophy. Further investigation in long-term isoflavone intake is required especially among neonates. The results suggest that the safety evaluation of the consumption of isoflavone should be based on isoflavone glycoside but not aglycone.
authors.affiliation: Department of Environmental Medicine, Center for Community Medicine, Jichi Medical School, Minamikawachi-machi, Tochigi 329-0498, Japan.
authors.forename: Jian-hong
authors.initials: JH
authors.lastname: Zhao
authors.forename: Yukitomo
authors.initials: Y
authors.lastname: Arao
authors.forename: Su-ju
authors.initials: SJ
authors.lastname: Sun
authors.forename: Atsumi
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Fujio
authors.initials: F
authors.lastname: Kayama
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000032:analysis / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007378:Interleukins / Q000378:metabolism; D007529:Isoflavones / Q000032:analysis / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D042282:Microdissection; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007378:Interleukins; D007529:Isoflavones; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C040641:genistin; D019833:Genistein