Effects of Ginkgo biloba extract on cell proliferation, cytokines and extracellular matrix of hepatic stellate cells.
OBJECTIVE
Hepatic fibrosis is the common wound-healing response to chronic liver injury. Ginkgo biloba extract (GbE) has been indicated to reverse hepatic fibrosis and exhibit therapeutic effects both in vitro and in vivo. This study aimed to investigate the underlying mechanism of GbE using HSC-T6 cells, a subline of hepatic stellate cells (HSC) as a model.


METHODS
HSC-T6 cells were seeded into six-well plates and allowed to attach overnight. After exposure to different concentrations of GbE761 for 24 or 48 h, cell cycle analysis, semiquantitative RT-PCR, Western blotting analysis and analysis of ECM secretion were performed.


RESULTS
It was revealed that GbE (1, 10, 100, 500 mg/l) suppressed HSC proliferation and caused G0/G1 phase arrest in a concentration-dependent manner. RT-PCR and Western blot assays were applied to detect the decline of transforming growth factor beta1(TGF-beta1) and connective tissue growth factor (CTGF) in both mRNA and protein levels after GbE treatment in HSC-T6 cells for 24 or 48 h. Meanwhile, GbE inhibited the synthesis of type I and type III collagens. Secretion of some extracellular matrix (ECM) proteins, such as type III procollagen (PC III), type IV collagen (collagen IV), laminin (LN), hyaluronic acid (HA), were all decreased in supernatant of GbE treated HSC cells.


CONCLUSIONS
Our results suggest that GbE confers its anti-fibrosis effects through inhibiting HSC proliferation, reducing TGF-beta1 and CTGF expression and consequently suppressing the collagen production and ECM secretion.
Zhang
Chunqing
C
Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan Shandong, China.
Zhu
Yuhua
Y
Wan
Jing
J
Xu
Hongwei
H
Shi
Henmei
H
Lu
Xiaoxia
X
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D055513:Connective Tissue Growth Factor; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D020441:Ginkgo biloba; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D000096983:Ginkgo Extract
D003094:Collagen; D055513:Connective Tissue Growth Factor; D016326:Extracellular Matrix Proteins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C526316:CCN2 protein, rat; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract