title: Active hexose correlated compound inhibits the expression of proinflammatory biomarker iNOS in hepatocytes.
abstract: OBJECTIVE
  Excess production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as proinflammatory biomarker in liver injury. The application of active hexose correlated compound (AHCC) as a functional food in complementary and alternative medicine has increased. The possibility that AHCC might inhibit iNOS induction was investigated as a potential liver-protective effect.
  
  
  METHODS
  Hepatocytes were isolated from rats by collagenase perfusion and cultured. Primary cultured hepatocytes were treated with interleukin-1β in the presence or absence of AHCC-sugar fraction (AHCC-SF).
  
  
  CONCLUSIONS
  AHCC-SF inhibited the production of NO and reduced expressions of iNOS mRNA and its protein. AHCC-SF had no effects on either IκB degradation or nuclear factor-κB (NF-κB) activation. In contrast, AHCC-SF inhibited the upregulation of type I interleukin-1 receptor (IL-1RI) through the inhibition of Akt phosphorylation. Transfection experiments with iNOS promoter-luciferase constructs revealed that AHCC-SF reduced the levels of iNOS mRNA at both promoter transactivation and mRNA stabilization steps. AHCC-SF inhibited the expression of iNOS gene antisense transcript, which is involved in iNOS mRNA stabilization. These findings demonstrate that AHCC-SF suppresses iNOS gene expression through a IκB/NF-κB-independent but Akt/IL-1RI-dependent pathway, resulting in the reduction of NO production. AHCC-SF may have therapeutic potential for various liver injuries.
authors.affiliation: Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsui
authors.forename: T
authors.initials: T
authors.lastname: Ozaki
authors.forename: M
authors.initials: M
authors.lastname: Oishi
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Kaibori
authors.forename: M
authors.initials: M
authors.lastname: Nishizawa
authors.forename: T
authors.initials: T
authors.lastname: Okumura
authors.forename: A-H
authors.initials: AH
authors.lastname: Kwon
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D011134:Polysaccharides; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C499366:Active Hexose Correlated Compound