title: Graptopetalum paraguayense ameliorates chemical-induced rat hepatic fibrosis in vivo and inactivates stellate cells and Kupffer cells in vitro.
abstract: BACKGROUND
  Graptopetalum paraguayense (GP) is a folk herbal medicine with hepatoprotective effects that is used in Taiwan. The aim of this study was to evaluate the hepatoprotective and antifibrotic effects of GP on experimental hepatic fibrosis in both dimethylnitrosamine (DMN)- and carbon tetrachloride (CCl(4))-induced liver injury rats.
  
  
  METHODS
  Hepatic fibrosis-induced rats were fed with the methanolic extract of GP (MGP) by oral administration every day. Immunohistochemistry, biochemical assays, and Western blot analysis were performed. The effects of MGP on the expression of fibrotic markers and cytokines in the primary cultured hepatic stellate cells (HSCs) and Kupffer cells, respectively, were evaluated.
  
  
  RESULTS
  Oral administration of MGP significantly alleviated DMN- or CCl(4)-induced liver inflammation and fibrosis. High levels of alanine transaminase, aspartate transaminase, bilirubin, prothrombin activity and mortality rates also decreased in rats treated with MGP. There were significantly decreased hydroxyproline levels in therapeutic rats compared with those of the liver-damaged rats. Collagen I and alpha smooth muscle actin (α-SMA) expression were all reduced by incubation with MGP in primary cultured rat HSCs. Furthermore, MGP induced apoptotic cell death in activated HSCs. MGP also suppressed lipopolysaccharide-stimulated rat Kupffer cell activation by decreasing nitric oxide, tumor necrosis factor-α and interleukin-6 production, and increasing interleukin-10 expression.
  
  
  CONCLUSIONS
  The results show that the administration of MGP attenuated toxin-induced hepatic damage and fibrosis in vivo and inhibited HSC and Kupffer cell activation in vitro, suggesting that MGP might be a promising complementary or alternative therapeutic agent for liver inflammation and fibrosis.
authors: Institute of Systems Biology and Bioinformatics, National Central University, Jhongli City, Taiwan.
authors: Li-Jen
authors: LJ
authors: Su
authors: Chia-Chuan
authors: CC
authors: Chang
authors: Chih-Hsueh
authors: CH
authors: Yang
authors: Shur-Jong
authors: SJ
authors: Hsieh
authors: Yi-Chin
authors: YC
authors: Wu
authors: Jin-Mei
authors: JM
authors: Lai
authors: Tzu-Ling
authors: TL
authors: Tseng
authors: Chi-Ying F
authors: CY
authors: Huang
authors: Shih-Lan
authors: SL
authors: Hsu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004128:Dimethylnitrosamine / Q000009:adverse effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology; D029624:Ferns / Q000737:chemistry*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013154:Spleen / Q000187:drug effects
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D004128:Dimethylnitrosamine