Procyanidin B2 inhibits the activation of hepatic stellate cells and angiogenesis via the Hedgehog pathway during liver fibrosis

BACKGROUND: Liver fibrosis is a wound‐healing process of liver featured by the over‐deposition of extracellular matrix (ECM) and angiogenesis. However, the effective treatment is lacking. Procyanidin B2 (PB2) is a flavonoid extract abundant in grape seeds with anti‐oxidant, anti‐inflammatory and anti‐cancer properties. The present study aimed to determine effects of PB2 on liver fibrosis. METHOD: The CCl4‐induced mouse liver fibrosis model and a human hepatic stellate cell (HSC) line (LX2 cells) were used to study the activation, ECM production and angiogenesis of HSCs through Western blotting analysis, immunohistochemistry, immunofluorescence staining, flow cytometry and tubulogenesis assay. A Hedgehog (Hh) pathway inhibitor (cyclopamine) and Smoothened agonist (SAG) were used to investigate the role of PB2 on Hh pathway. RESULTS: The results showed that PB2 could inhibit the proliferation and induce apoptosis of HSCs. PB2 could also down‐regulate the expressions of VEGF‐A, HIF‐1α, α‐SMA, Col‐1 and TGF‐β1 of HSCs in vivo and in vitro. The application of SAG and cyclopamine proved that PB2 targets on Hh pathway. CONCLUSIONS: PB2 inhibited the Hh pathway to suppress the activation, ECM production and angiogenesis of HSCs, therefore reverses the progression of liver fibrosis in vivo and in vitro.