Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor.
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.
Wang
Guei-Jane
GJ
National Research Institute of Chinese Medicine, Taipei, Taiwan.
Huang
Yeh-Jeng
YJ
Chen
Deng-Hai
DH
Lin
Yun-Lian
YL
D000818:Animals; D017209:Apoptosis; D000077214:Becaplermin; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020940:Reishi / Q000737:chemistry*; D014315:Triterpenes / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014315:Triterpenes; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor