title: Glycyrrhetinic acid suppressed NF-κB activation in TNF-α-induced hepatocytes.
abstract: Tumor necrosis factor-alpha (TNF-α) is a crucial inflammatory cytokine when hepatocytes are damaged. Glycyrrhiza uralensis Fisch. (Chinese licorice) has been widely used in Chinese herbal prescriptions for the treatment of liver diseases and as a food additive. Nuclear factor-kappa B (NF-κB) reporter gene assay in TNF-α-induced HepG2 was used as a screening platform. IκBα phosphorylation and p65 translocation were measured by Western blotting, and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression were further confirmed in rat primary hepatocytes. Results showed that TNF-α enhanced NF-κB activity was significantly attenuated by glycyrrhetinic acid in a concentration-dependent manner in the NF-κB reporter gene assay. Glycyrrhetinic acid decreased the gene expression of iNOS through inhibited IκBα phosphorylation and p65 translocation in protein level. Furthermore, NO production and iNOS expression were reduced by glycyrrhetinic acid in TNF-α-induced rat primary hepatocytes. These results suggest that glycyrrhetinic acid may provide hepatoprotection against chronic liver inflammation through attenuating NF-κB activation to alleviate the inflammation.
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare , Taipei, Taiwan.
authors.forename: Hong-Jhang
authors.initials: HJ
authors.lastname: Chen
authors.forename: Shih-Pei
authors.initials: SP
authors.lastname: Kang
authors.forename: I-Jung
authors.initials: IJ
authors.lastname: Lee
authors.forename: Yun-Lian
authors.initials: YL
authors.lastname: Lin
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D020672:I-kappa B Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D006034:Glycyrrhetinic Acid
keywords: Glycyrrhiza uralensis; NF-κB; TNF-α; glycyrrhetinic acid; hepatocytes