PMID- 22103576
OWN - NLM
STAT- MEDLINE
DCOM- 20120927
LR  - 20131121
IS  - 1365-2362 (Electronic)
IS  - 0014-2972 (Linking)
VI  - 42
IP  - 6
DP  - 2012 Jun
TI  - Protective effects of kaerophyllin against liver fibrogenesis in rats.
PG  - 607-16
LID - 10.1111/j.1365-2362.2011.02625.x [doi]
AB  - 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. MATERIALS AND 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 alpha (TNF-alpha) in vitro. Peroxisome 
      proliferator-activated receptor-gamma (PPAR-gamma) expression was knocked down in rat 
      HSCs using PPAR-gamma 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-alpha, interleukin-1beta (IL-1beta) and monocyte chemoattractant protein-1 (MCP-1) 
      genes. In HSCs, kaerophyllin elevated PPAR-gamma activity and reduced 
      TNF-alpha-stimulated mRNA levels of intracellular adhesion molecule-1 (ICAM-1), MCP-1 
      and IL-1beta genes, which were reversed by small interfering RNA knockdown of PPAR-gamma 
      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-gamma 
      expression.
CI  - (c) 2011 The Authors. European Journal of Clinical Investigation (c) 2011 Stichting 
      European Society for Clinical Investigation Journal Foundation.
FAU - Lee, Ting-Fang
AU  - Lee TF
AD  - Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Lin, Yun-Lian
AU  - Lin YL
FAU - Huang, Yi-Tsau
AU  - Huang YT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111122
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Carcinogens)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Lignans)
RN  - 0 (Plant Extracts)
RN  - 0 (kaerophyllin)
RN  - 075T165X8M (Thioacetamide)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Carcinogens/metabolism
MH  - Drugs, Chinese Herbal/*therapeutic use
MH  - Hepatic Stellate Cells/*drug effects/metabolism
MH  - Lignans/*therapeutic use
MH  - Liver/*drug effects/metabolism
MH  - Liver Cirrhosis/chemically induced/drug therapy/*prevention & control
MH  - Male
MH  - Plant Extracts/metabolism/therapeutic use
MH  - Plant Roots
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thioacetamide/*adverse effects/metabolism
EDAT- 2011/11/23 06:00
MHDA- 2012/09/28 06:00
CRDT- 2011/11/23 06:00
PHST- 2011/11/23 06:00 [entrez]
PHST- 2011/11/23 06:00 [pubmed]
PHST- 2012/09/28 06:00 [medline]
AID - 10.1111/j.1365-2362.2011.02625.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2012 Jun;42(6):607-16. doi: 10.1111/j.1365-2362.2011.02625.x. 
      Epub 2011 Nov 22.