Danshensu inhibits acetaldehyde-induced proliferation and activation of hepatic stellate cell-T6.
OBJECTIVE
To evaluate the effects of danshensu, the main component of the extract of Chinese medicine Salvia miltiorrhiza, on the proliferation and activation of hepatic stellate cells (HSCs).


METHODS
The activation of HSC-T6 was induced by exposure to acetaldehyde. In the meantime, different doses of danshensu were added to the culture medium. After 24 h of treatment with danshensu in acetaldehyde, the viability of HSC-T6 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cell cycle was determined through flow cytometry, and the gene transcription levels of plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β1 (TGF-β1), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2) were analyzed by real-time quantitative polymerase chain reaction.


RESULTS
The proliferation of HSCs induced by 200 μmol/L acetaldehyde could be significantly inhibited by danshensu, and the percentage of HSCs in S phase was significantly increased as compared with the control cells (P<0.05), which were respectively evidenced by MTT assay and flow cytometry. Danshensu down-regulated the mRNA expression of TGF-β1 and PAI-1 and up-regulated the uPA transcription level (P<0.01), while the transcription level of MMP-2 was not significantly affected in HSC-T6.


CONCLUSIONS
Danshensu can inhibit the proliferation and activation of HSC-T6, as well as regulate some cytokines involved in extracellular matrix accumulation, which offers a potential therapeutic alternative for liver fibrosis.
Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, China.
Li
L
Zhang
Tao
T
Wu
Jun-ming
JM
Chen
Li-li
LL
Yang
Hai-yan
HY
Song
Guang
G
Ji
D000079:Acetaldehyde / Q000009:adverse effects*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D007773:Lactates / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D007773:Lactates; D017395:Plasminogen Activator Inhibitor 1; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C035055:3,4-dihydroxyphenyllactic acid; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D000079:Acetaldehyde