title: Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes.
abstract: BACKGROUND
  Hepatic stellate cells (HSCs), the key cell type for hepatic fibrosis, become activated and profibrogenic in the presence of hepatocyte apoptotic bodies (ABs). Bupleurum scorzonerifolium (BS), a widely used traditional Chinese herb for liver diseases, was fractionated, and the inhibitory effects of BS extracts on AB-induced HSC migration were screened. The activity-guided fractionation led to a lignan, kaerophyllin. In this study, the anti-fibrotic effects of kaerophyllin were studied in the presence of ABs.
  
  
  METHODS
  LX-2 cells phagocytosing ultraviolet (UV)-induced HepG2 ABs were investigated by confocal microscopy and flow cytometry. AB-induced HSC activation was evaluated by immunoblotting and real-time PCR analyses. HSC migration was measured by wound-healing assays.
  
  
  RESULTS
  HepG2 ABs induced LX-2 activation, with the production of collagen I and α-smooth muscle actin, upregulated profibrogenic gene transcriptions and increased NF-κB activity, cell migration and phagocytosis. Kaerophyllin from BS antagonized AB-induced HSC migration and activation.
  
  
  CONCLUSIONS
  Kaerophyllin inhibited AB-induced LX-2 activation and migration with downregulation of Akt/ERK phosphorylations and NF-κB activity. Our study suggests a novel platform for screening anti-fibrotic compounds with ABs.
authors: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Ting-Fang
authors: TF
authors: Lee
authors: Yun-Lian
authors: YL
authors: Lin
authors: Yi-Tsau
authors: YT
authors: Huang
mesh_terms: D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D015153:Blotting, Western; D029972:Bupleurum / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005355:Fibrosis; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D010587:Phagocytosis; D010936:Plant Extracts / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000199:Actins; C051274:Bupleurum root extract; D024042:Collagen Type I; D017705:Lignans; D016328:NF-kappa B; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; C559527:kaerophyllin; D051058:Oncogene Protein v-akt; D009219:Myosin-Light-Chain Kinase; D048049:Extracellular Signal-Regulated MAP Kinases