Inhibitory effects of Ligusticum chuanxiong on the proliferation of rat hepatic stellate cells.
OBJECTIVE
Platelet-derived growth factor (PDGF) is a very potent mitogen for hepatic stellate cells (HSC) in hepatic fibrogenesis. Ligusticum chuanxiong Hort. (LC), a traditional Chinese herb used for cerebrovascular diseases, has been shown to exert anti-inflammatory and free radical scavenging effects. The aims of the present study were to investigate the effects of LC extract on the proliferation-related biomarkers in a rat HSC cell line (HSC-T6) stimulated with PDGF.


METHODS
DNA synthesis via bromodeoxyuridine (BrdU) incorporation, cell cycle related proteins and apoptosis markers were determined to evaluate the inhibitory effects of LC.


RESULTS
The results revealed that LC extract (25-100 microg/mL) concentration-dependently decreased the PDGF-induced cell proliferation as well as alpha-smooth muscle actin expression in HSC. The inhibitory activity of LC on HSC was associated with: (i) inhibition of BrdU incorporation; (ii) induction of apoptosis with the activation of caspase-3, up-regulation of cell cycle inhibitory proteins p21 and p27, and down-regulation of cell cycle stimulatory proteins cyclins D1 and D2; and (iii) increased phosphorylation of mitogen-activated protein kinases (JNK). LC at the studied concentrations showed no direct cytotoxicity on primary hepatocytes.


CONCLUSIONS
The results suggest that LC significantly inhibited PDGF-activated HSC proliferation, possibly through apoptotic mechanisms and the potential of LC as an antifibrotic agent warrants further investigation.
Lin
Yun-Lian
YL
National Research Institute of Chinese Medicine, National Yang-Ming University, Taipei, Taiwan.
Lee
Ting-Fang
TF
Huang
Yeh-Jeng
YJ
Huang
Yi-Tsau
YT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000032:analysis; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005434:Flow Cytometry; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D030004:Ligusticum; D008516:Medicine, Chinese Traditional; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage; D051381:Rats
D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D010982:Platelet-Derived Growth Factor; C505410:Casp3 protein, rat; D053148:Caspase 3; C101574:chuangxiong extract