Background: Hesperetin, a natural component of citrus fruits, is indicated to
have beneficial anti-inflammatory effects on injury and various cancers as a transforming
growth factor beta (TGF-β) inhibitor. However, little evidence associates hesperetin with
Objective: Work from our laboratory aims at finding the mechanism by which hesperetin
attenuates liver fibrosis.
Methods: Bile duct ligation (BDL) was used to induce liver fibrosis in mice and the
findings were determined using enzyme-linked immunosorbent assay, quantitative realtime
polymerase chain reaction, western blotting and immunohistochemical staining.
Results: Data from Immunohistochemical staining and injury score indicated that
pathological lesions were reduced by hesperetin treatment. Decreasing levels of several
serum parameters including cytokines tumor necrosis factor-α (TNF-α), and interleukin-6
(IL-6), liver enzyme alanine aminotransferase (ALT) and aspartate aminotransferase
(AST), fibrosis indicators laminin (LN), hyaluronic acid (HA) and hydroxylproline (Hyp)
suggested similar results to the immunohistochemical. In addition, our data verified
hesperetin could suppress the formation of extracellular matrix and hepatocyte
apoptosis in vitro, together with promoting hepatic stellate cell death in vivo, which was
considered to be associated with the inhibition of TGF-β1/Smad pathways.
Conclusion: In the present study, the favorable role of hesperetin extracted from citrus
peels was verified to prevent the progression of BDL-induced liver fibrosis via inhibiting
TGF-β1/Smad pathway-mediated extracellular matrix progression and apoptosis.