Epithelial-mesenchymal transition (EMT) occurs in the development of
fibrosis and
carcinogenesis. EMT is associated with chronic liver injury. Evidence shows that hepatocytes undergo EMT in the adult liver. The
Qinggan Huoxue Recipe (QGHXR), a Traditional Chinese Medicinal formula, shows a range of pharmacological effects in treating
alcoholic liver disease. The present study aimed to investigate the effect of four major components of QGHXR,
baicalin, salvianic
acid,
puerarin and saikosaponin, on EMT in vitro, and to elucidate the potential mechanism of QGHXR against EMT via the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway. EMT models were established using LO2 hepatocytes and HepG2 cells treated with
acetaldehyde in vitro.
Acetaldehyde presented a mesenchymal cell characteristic in hepatocytes, accompanied by an increased expression of mesenchymal markers, including
vimentin and
fibronectin, and decreased
E-cadherin.
Baicalin and
puerarin abrogated the increased expression of
vimentin and
fibronectin, and rescued
E-cadherin expression in
acetaldehyde-treated hepatocytes. It was further demonstrated that
baicalin and
puerarin reduced the gene expression of snail, TGF-β1 and Smad3. A decreased expression of tight function markers, including ZO-1,
occludin and
claudin, were also found in the
acetaldehyde-treated hepatocytes. Barcacin regulated the
mRNA level of TGF-βl and snail, and then suppressed the EMT process. This was accompanied by an increased
mRNA level of
E-cadherin and decreased levels of
vimentin and
fibronectin, but no significant differences in of Smad3,
occludin, ZO-1 and
claudin were observed.
Puerarin regulated the
mRNA level of TGF-βl, Smad3 and snail, suppresing the EMT process, which was accompanied by an increased
mRNA level of
E-cadherin and decreased levels of
vimentin and
fibronectin, along with increased levels of
occludin, ZO-1 and
claudin. When the snail gene was silent, barcacin and
puerarin did not show significant effects in the
acetaldehyde-treated cells. The results presented a novel mechanism through which
baicalin and
puerarin modulated hepatocyte EMT to improve
liver fibrosis.