Butein suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture.
Hepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis. In this study, we investigate the inhibitory effect of butein on the activation and proliferation of rat primary cultured hepatic stellate cells. Possible cytotoxic effects were measured on stellate cells and hepatocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of butein on the production of collagen and smooth muscle alpha-actin proteins were examined at the same concentration, by western blot. The effects of butein on alpha1(I) collagen, tissue inhibitor of metalloproteinase-1, and metalloproteinase-13 gene expression in activated stellate cells were investigated by measuring mRNA levels using reverse transcription polymerase chain reaction. The effect of butein on DNA synthesis was also determined. Butein, at a concentration of 1 microg mL(-1), reduced DNA synthesis without affecting cell viability, and downregulated smooth muscle alpha-actin and type-I collagen expression, and alpha1(I) collagen and tissue inhibitor of metalloproteinase-1 mRNA expression, while treatment with butein induced metalloproteinase-13 mRNA expression. These findings suggest that butein is a potent inhibitor of stellate cell transformation.
Woo
Sun Wook
SW
Department of Pharmacy, Medicinal Resources Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
Lee
Sung Hee
SH
Kang
Hee-Chul
HC
Park
Eun-Jeon
EJ
Zhao
Yu-Zhe
YZ
Kim
Youn-Chul
YC
Sohn
Dong Hwan
DH
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000963:Antimetabolites; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D003094:Collagen / Q000096:biosynthesis; D017364:Collagenases / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008297:Male; D053509:Matrix Metalloproteinase 13; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
D000199:Actins; D000963:Antimetabolites; D047188:Chalcones; D010726:Phosphodiesterase Inhibitors; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C040918:butein; D002599:Chalcone; D003094:Collagen; D004247:DNA; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D001973:Bromodeoxyuridine