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 PDGFbeta-receptor (PDGFbetaR), Akt and JNK. The results indicated that the GLT attenuated BrdU incorporation in a concentration-dependent manner with an IC(50) of 8.52 +/- 0.33 microg/mL. The inhibitory effect of the GLT was associated with downregulation of cyclins D1 and D2, and PDGFbetaR and Akt phosphorylation, upregulation of JNK phosphorylation, and a reduction in alpha-SMA expression. These results indicated that G. lucidum inhibits PDGF-BB-activated HSC proliferation possibly through blocking PDGFbetaR phosphorylation, thereby indicating its efficacy for preventing and treating hepatic fibrosis.
(c) 2008 John Wiley & Sons, Ltd.