title: Gomisin N in the herbal drug gomishi (Schisandra chinensis) suppresses inducible nitric oxide synthase gene via C/EBPβ and NF-κB in rat hepatocytes.
abstract: Gomishi is the dried fruit of Schisandra chinensis Baillon (Fructus Schisandrae chinensis, FSC) and has been used in Japanese Kampo medicine to treat inflammatory and liver diseases. However, it is unclear which constituent of FSC is primarily responsible for its pharmacological effects. FSC was extracted with methanol, fractionated by hydrophobicity, and further purified. We measured the effects of each fraction or constituent thereof on the induction of the inflammatory mediator nitric oxide (NO), which was induced by interleukin 1β in primary cultured rat hepatocytes. The hydrophobic fraction markedly suppressed NO induction and reduced the expression of inducible nitric oxide syntheses (iNOS) in interleukin 1β-treated hepatocytes. Gomisin N and γ-schizandrin, two major constituents of the hydrophobic fraction, significantly reduced NO production and the levels of the iNOS protein, mRNA, and antisense transcript. Gomisin N and γ-schizandrin also decreased the transcription of interleukin 1β and inflammatory chemokines. The overexpression of the p65 subunit of nuclear factor κB or CCAAT/enhancer-binding protein β increased the promoter activity of the iNOS gene in the firefly luciferase assay, whereas gomisin N decreased the promoter activity. The anti-inflammatory activity of FSC and its constituents were analysed, and we demonstrated that gomisin N and γ-schizandrin are involved in the hepatoprotective effect of the FSC extract, which has therapeutic potential for liver disease.
authors.affiliation: Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Takimoto
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Qian
authors.forename: Emi
authors.initials: E
authors.lastname: Yoshigai
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Okumura
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Ikeya
authors.forename: Mikio
authors.initials: M
authors.lastname: Nishizawa
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002478:Cells, Cultured; D034242:Cyclooctanes / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics*; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D032141:Schisandra / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D034242:Cyclooctanes; D017705:Lignans; D016328:NF-kappa B; D011083:Polycyclic Compounds; C015499:schizandrin B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II