title: Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor.
abstract: 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.
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan.
authors.forename: Guei-Jane
authors.initials: GJ
authors.lastname: Wang
authors.forename: Yeh-Jeng
authors.initials: YJ
authors.lastname: Huang
authors.forename: Deng-Hai
authors.initials: DH
authors.lastname: Chen
authors.forename: Yun-Lian
authors.initials: YL
authors.lastname: Lin
mesh_terms: 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
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014315:Triterpenes; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor