Autophagy has been regarded as an
inflammation-associated defensive mechanism against chronic
liver disease, which has been highlighted as a novel therapeutic target for the treatment of
liver fibrosis. We herein aimed to study the effects of
catalpol on
liver fibrosis in vivo and in vitro, and to elucidate the role of autophagy in
catalpol-induced anti-
inflammation.
Catalpol protected the liver against CCl4-induced injury, as evidenced by mitigated hepatic steatosis,
necrosis, and fibrotic septa.
Catalpol decreased the serum levels of
alkaline phosphatase,
alanine aminotransferase,
aspartate aminotransferase and
bilirubin as well as the liver/
body weight ratio. Masson and sirius red staining along with
hydroxyproline detection showed that
catalpol decreased
collagen deposition significantly compared to that of the model group.
Catalpol inhibited CCl4-induced
liver fibrosis, manifested as decreased expressions of α-SMA,
fibronectin and α1(I)-procollagen at both transcriptional and translational levels. Inflammatory factors, such as IL-1β, TNF-α,
IL-18,
IL-6 and COX-2, were significantly elevated in rats receiving CCl4 and down-regulated by
catalpol in a dose-dependent manner in vivo. Western blot and immunofluorescence assay revealed that
catalpol activated the autophagy of rats with CCl4-caused
liver fibrosis, as indicated by up-regulation of LC3-II and
beclin1 and down-regulation of P62. The results of in vitro experiments were consistent. Interestingly, inhibition or depletion of autophagy by
LY294002 or Atg5
siRNA significantly attenuated
catalpol-induced anti-inflammatory effects on activated hepatic stellate cells in vitro. In conclusion,
catalpol relieved
liver fibrosis mainly by inhibiting
inflammation, and autophagy inhibition attenuated the
catalpol-induced anti-inflammatory effect on
liver fibrosis.