Oleoylethanolamide (OEA), an
endocannabinoid-like molecule, was revealed to modulate lipid metabolism through a
peroxisome proliferator-activated receptor-α (
PPAR-α) mediated mechanism. In present study, we further investigated the activities and mechanisms of OEA in ameliorating hepatic
fibrosis in Sv/129 mice induced by a
methionine choline-deficient (MCD) diet or
thioacetamide (TAA) treatment.
Liver fibrosis development was assessed by
Hematoxylin-
eosin and Sirius red staining. Treatment with OEA (5 mg/kg/day,
intraperitoneal injection, i.p.) significantly attenuated the progress of
liver fibrosis in both two experimental animal models by blocking the activation of hepatic stellate cells (HSCs). Gene expression analysis of hepatic tissues indicated that OEA inhibited the expression of α-smooth muscle action (α-SMA) and
collagen matrix,
fibrosis markers, and genes involved in
inflammation and extracellular matrix remodeling. In vitro studies showed that OEA inhibited
transforming growth factor β1-stimulated HSCs activation through suppressing Smad2/3 phosphorylation, α-SMA expression and myofibroblast transformation. These improvements could not be observed in
PPAR-α knockout mice models with OEA administration, which suggested all the anti-fibrotic effects of OEA in vivo and in vitro were mediated by
PPAR-α activation. Collectively, our results suggested that OEA exerted a pharmacological effect on modulating hepatic
fibrosis development through the inhibition of HSCs activation in liver and therefore may be a potential therapeutic agent for
liver fibrosis.