title: Exploration of Emodin to treat alpha-naphthylisothiocyanate-induced cholestatic hepatitis via anti-inflammatory pathway.
abstract: Emodin, 1,3,8-trihydroxy-6-methyl-anthraquinone, is an anthraquinone derivative from the roots of Rheum officinale Baill that has been used to treat many diseases in digestive system for thousands of years. This study is to disclose the mechanism of Emodin to treat cholestatic hepatitis via anti-inflammatory pathway. Rats were divided into Emodin, ursodeoxycholic acid, Dexamethasone, model and blank control groups with treatment of respective agent after administration of alpha-naphthylisothiocyanate. At 24 h, 48 h and 72 h time points after administration, liver function, pathological changes of hepatic tissue, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), cytokine-induced neutrophil chemoattractant (CINC)-1, macrophage inflammatory protein (MIP)-2, intercellular adhesion molecule (ICAM)-1, nuclear factor (NF)-kappaB and early growth response (Egr)-1, nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were detected. As a result, compared to the controls, Emodin had a notable effect on rat's living condition, pathological manifestation of hepatic tissue, total bilirubin, direct bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P<0.05), but had little effect on alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and total bile acid. With Emodin intervention, levels of TNF-alpha, IL-6, MPO, MDA, CINC-1, MIP-2, ICAM-1 and translocation of NF-kappaB were remarkably decreased, and levels of NO and iNOS were markedly increased (P<0.05). Emodin had no effect on Egr-1. In conclusion, Emodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis by anti-inflammation. The effects are mainly due to antagonizing pro-inflammatory cytokines and mediators, inhibiting oxidative damage, improving hepatic microcirculation, reducing impairment signals, and controlling neutrophil infiltration.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Mei
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Zhang
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Huang
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Duan
authors.forename: Pian
authors.initials: P
authors.lastname: Ye
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051766:Early Growth Response Protein 1 / Q000032:analysis; D004642:Emodin / Q000627:therapeutic use*; D006505:Hepatitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D015850:Interleukin-6; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D008315:Malondialdehyde; D015058:1-Naphthylisothiocyanate; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D004642:Emodin