title: Protective effects of kaerophyllin against liver fibrogenesis in rats.
abstract: BACKGROUND
  We previously demonstrated that kaerophyllin, a lignan, isolated from a widely used traditional Chinese herb, Bupleurum scorzonerifolium, leading to the inhibition of hepatic stellate cells (HSCs) activation in vitro. This current study evaluated the in vivo role of kaerophyllin in protecting the liver against injury and fibrogenesis caused by thioacetamide (TAA) in rats and further explored the underlying mechanisms.
  
  
  METHODS
  Liver fibrosis in Sprague-Dawley rats was induced by intraperitoneal injection of TAA (200 mg/kg) twice per week for 6 weeks. Animals were divided into five groups: vehicle control, TAA control, TAA + low dose kaerophyllin, TAA + high dose kaerophyllin and TAA + curcumin groups. Kaerophyllin (10 or 30 mg/kg) or curcumin (150 mg/mL) was given by gavage twice per day consecutively for 4 weeks starting 2 weeks after TAA injection. Rat HSCs were used to investigate the anti-inflammatory role of kaerophyllin against tumour necrosis factor α (TNF-α) in vitro. Peroxisome proliferator-activated receptor-γ (PPAR-γ) expression was knocked down in rat HSCs using PPAR-γ small interfering RNAs.
  
  
  RESULTS
  Kaerophyllin significantly protected liver from injury by reducing serum aspartate transaminase and alanine transaminase levels and by improving the histological architecture and fibrosis score. In addition, kaerophyllin suppressed inflammation by reducing the mRNA of TNF-α, interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) genes. In HSCs, kaerophyllin elevated PPAR-γ activity and reduced TNF-α-stimulated mRNA levels of intracellular adhesion molecule-1 (ICAM-1), MCP-1 and IL-1β genes, which were reversed by small interfering RNA knockdown of PPAR-γ gene.
  
  
  CONCLUSIONS
  Our results demonstrated that kaerophyllin protected the rat liver from TAA-caused injury and fibrogenesis by suppressing hepatic inflammation and inhibiting HSC activation, possibly through upregulation of PPAR-γ expression.
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: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D017705:Lignans / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D010936:Plant Extracts / Q000378:metabolism / Q000627:therapeutic use; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D002273:Carcinogens; D004365:Drugs, Chinese Herbal; D017705:Lignans; D010936:Plant Extracts; C559527:kaerophyllin; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase