title: Paeoniflorin regulates macrophage activation in dimethylnitrosamine-induced liver fibrosis in rats.
abstract: BACKGROUND
  Macrophages in other organs (e.g. kidneys, lungs, and spleen, et. al) have rarely been reported in the development of liver fibrosis. Therefore, it is important to investigate macrophage activation in the main organs in liver fibrosis. We investigated the potential antifibrogenic effects of paeoniflorin (PF) in a dimethylnitrosamine (DMN)-induced rat model with special focus on inhibiting macrophage activation in the main organs.
  
  
  METHODS
  Rat hepatic fibrosis was induced by treatment with DMN three times weekly over a 4-week period. DMN rats were treated with water, PF, or gadolinium chloride (GdCl3) from the beginning of the 3rd week. The expression of CD68, marker of macrophage, was investigated using immunohistochemical, real-time PCR, and western blot analysis.
  
  
  RESULTS
  Hepatic hydroxyproline content markedly decreased and histopathology improved in the DMN-PF rats. Expression of desmin and collagen 1 decreased notably in DMN-PF liver. CD68 expression in the liver, spleen and kidney increased markedly after 2 weeks but decreased in DMN-water rats. PF and GdCl3 decreased CD68 expression in the liver and spleen and there was no effect on kidney. CD68 expression in the lung increased gradually during the course of DMN-induced liver fibrosis, and PF inhibited CD68 expression in the lung significantly while GdCl3 increased CD68 markedly. Expression of tumor necrosis factor (TNF-α) was decreased significantly by GdCl3 in the liver, as revealed by real-time PCR analysis. However, GdCl3 could not decrease TNF-α level in the serum by enzyme linked immunosorbent assay (ELISA).
  
  
  CONCLUSIONS
  Macrophage activation was disrupted in the liver, spleen, lung and kidney during development of DMN-induced liver fibrosis. PF administration attenuated DMN-induced liver fibrosis at least in part by regulating macrophage disruption in the main organs.
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, 2901 Caolang Road, Jin Shan District, Shanghai, 201508, China. xiaorong3chen@yahoo.com.cn
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Lu
authors.forename: Zongguo
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.forename: Qingnian
authors.initials: Q
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.forename: Lingqing
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006909:Hydroxyproline / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D039821:Monoterpenes; D029596:Paeonia / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule; D006027:Glycosides
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001565:Benzoates; D001952:Bridged-Ring Compounds; D024042:Collagen Type I; D003893:Desmin; D004128:Dimethylnitrosamine; D005960:Glucosides; D006909:Hydroxyproline; D039821:Monoterpenes; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C015423:peoniflorin; D006027:Glycosides