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Ganoderma lucidum Extract Attenuates the Proliferation of Hepatic Stellate Cells by Blocking the PDGF Receptor

  作者 Wang, GJ; Huang, YJ; Chen, DH; Lin, YL  
  选自 期刊  Phytotherapy Research;  卷期  2009年23-6;  页码  833-839  
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[摘要]Hepatic fibrosis is an outcome of chronic liver diseases. The activation and proliferation of hepatic stellate cells (HSCs) is a key event in liver injury. The fruiting body of Ganoderma lucidum has long been a popular oriental medicine for treating liver diseases. The aim of this present study was to investigate the antiproliferative effects of the triterpenoid-rich extract (GLT) of G. lucidum in a cell line of rat HSCs (HSC-T6) stimulated with platelet-derived growth factor (PDGF)-BB. DNA synthesis was investigated by bromodeoxyuridine (BrdU) incorporation. Flow cytometry using propidium iodide (PI) labeling was carried out to analyse the cell cycle distribution and apoptosis. alpha-Smooth muscle actin (alpha-SMA) was used to evaluate extracellular matrix deposition, and western blotting was performed to measure cyclins D1 and D2, and phosphorylation of the PDGF beta-receptor (PDGF beta R), Akt and JNK. The results indicated that the GLT attenuated BrdU incorporation in a concentration-dependent manner with an IC50 of 8.52 +/- 0.33 mu g/mL. The inhibitory effect of the GLT was associated with downregulation of cyclins D1 and D2, and PDGF beta R and Akt phosphorylation, upregulation of JNK phosphorylation, and a reduction in a-SMA expression. These results indicated that G. lucidum inhibits PDGF-BB-activated HSC proliferation possibly through blocking PDGF beta R phosphorylation, thereby indicating its efficacy for preventing and treating hepatic fibrosis. Copyright (c) 2008 John Wiley & Sons, Ltd.

 
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