The protective effects of Mallotus furetianus extract (MF) on
liver fibrosis induced with
ethanol were examined using in vivo and in vitro model. MF treatment suppressed plasma
alanine aminotransferase and
aspartate aminotransferase activities in
ethanol plus
carbon tetrachloride (CCl4)-induced
cirrhosis rat model. MF also suppressed the increase in type l
collagen and α-smooth muscle actin expression in the livers of
ethanol plus CCl4-induced rat by the maintenance of intracellular
glutathione levels. Furthermore, we evaluated the effect of MF on the alcohol-induced activation of hepatic stellate cells (HSCs), which are responsible for the increased production and deposition of the extracellular matrix in liver injury. Here, we observed the enhancement of the intracellular
reactive oxygen species (ROS) levels and the increase in
type I collagen and a-SMA expression in HSCs activated with
ethanol. However, the enhanced ROS levels were suppressed with the treatments of MF or
diphenyleneiodonium (DPI). Furthermore, the treatment of MF or DPI suppressed the increase in
type I collagen and a-SMA expression activated with
ethanol. We also observed that the treatment of MF or LY194002 suppressed the increase in
type I collagen expression in HSCs activated with
ethanol, suggesting that
ethanol induced
type I collagen expression via the PI3K-Akt signaling pathway. On the other hand, the suppression of the synthesis of
type I collagen in
ethanol and MF-treated HSCs was inhibited by
H-89. From these results, MF may suppress the increase in the activity of
NADPH oxidase in HSCs activated with
ethanol through the cAMP-PKA pathway.