title: Japanese Kampo Saireito Has a Liver-Protective Effect Through the Inhibition of Inducible Nitric Oxide Synthase Induction in Primary Cultured Rat Hepatocytes.
abstract: Japanese herbal medicine, Kampo saireito, is used for treatments in patients with digestive diseases, including chronic hepatitis and cirrhosis. However, few studies demonstrate scientific evidence for liver-protective effects of saireito. In inflamed liver, proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β stimulate the induction of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production. Excessive levels of NO synthesized by iNOS have been implicated as one of the factors in liver injury, so it is essential to reduce the induction of iNOS for the prevention of liver injury. In this study, we examined IL-1β-stimulated hepatocytes as a simple "in vitro injury model" to investigate liver-protective effects of saireito.
  
  
  
  Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of saireito. The induction of NO production and iNOS and its signaling pathway were analyzed.
  
  
  
  Saireito inhibited the production of NO dose and time dependently and reduced the expression of iNOS messenger RNA (mRNA) and its protein. Saireito had no effect on IκB degradation but inhibited the translocation of nuclear factor (NF)-κB to the nucleus and its DNA binding. Saireito also inhibited the activation of Akt, resulting in the reduction of type I IL-1 receptor (IL-1RI) mRNA and protein expression.
  
  
  
  These findings demonstrate that saireito suppresses iNOS gene expression through the inhibition of NF-κB and IL-1RI-dependent pathways, leading to the reduction of NO production. Saireito may have therapeutic potential for organ injuries, including liver.
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Miki
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Tokuhara
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Oishi
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Richi
authors.initials: R
authors.lastname: Nakatake
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kaibori
authors.affiliation: Department of Biomedical Sciences, College of Life Sciences Ritsumeikan University, Kusatsu, Shiga, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan okumura@hirakata.kmu.ac.jp.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007564:Japan; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020835:Medicine, Kampo; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; C080903:sairei-to; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051057:Proto-Oncogene Proteins c-akt
keywords: inducible nitric oxide synthase; liver injury; nitric oxide; nuclear factor–κB; primary cultured hepatocytes; type I interleukin-1 receptor