Aloe emodin suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture.
We have studied the inhibitory effect of aloe emodin on hepatic stellate cells activation and proliferation, as these cells play a key role in the pathogenesis of hepatic fibrosis. Rat hepatic stellate cells were activated by contact with plastic dishes, resulting in their transformation into myofibroblast-like cells. Primary hepatic stellate cells were exposed to aloe emodin (1-10 microg/ml). 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 aloe emodin on production of type I collagen and smooth muscle cell alpha-actin were examined at the same concentration, by quantitative immunoprecipitation. Antiproliferative effects were examined by bromodeoxyuridine incorporation. Aloe emodin at 10 microg/ml restored the morphological changes characteristic of activated primary stellate cells, reduced DNA synthesis to 95% of control hepatic stellate cells at 10 microg/ml without affecting cell viability, and inhibited type I collagen production and smooth muscle alpha-actin expression by 86.77% and 99%, respectively, which suggest that aloe emodin 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.
Nan
Ji-Xing
JX
Lee
Sung Hee
SH
Park
Eun-Jeon
EJ
Zhao
Yu Zhe
YZ
Sohn
Dong Hwan
DH
D000199:Actins / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000378:metabolism
D000199:Actins; D000880:Anthraquinones; D024042:Collagen Type I; D004791:Enzyme Inhibitors; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D004247:DNA; C518327:aloe emodin; D001973:Bromodeoxyuridine; D004642:Emodin