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

Abstract

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.

• Authors: Jiao Feng, Chengfen Wang, Tong Liu, Jingjing Li, Liwei Wu, Qiang Yu, Sainan Li, Yuting Zhou, Jie Zhang, Jiaojiao Chen, Jie Ji, Kan Chen, Yuqing Mao, Fan Wang, Weiqi Dai, Xiaoming Fan, Jianye Wu, Chuanyong Guo
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 9 Pg. 6479-6493 (09 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 31328391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Biflavonoids
• Hedgehog Proteins
• Proanthocyanidins
• Transforming Growth Factor beta1
• Veratrum Alkaloids
• procyanidin B2
• Catechin
• Carbon Tetrachloride
• cyclopamine

Topics

• Animals
• Biflavonoids (pharmacology)
• Carbon Tetrachloride (pharmacology)
• Catechin (pharmacology)
• Cell Line
• Cell Proliferation (drug effects)
• Down-Regulation (drug effects)
• Hedgehog Proteins (metabolism)
• Hepatic Stellate Cells (drug effects, metabolism)
• Humans
• Liver (drug effects, metabolism)
• Liver Cirrhosis (drug therapy, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Morphogenesis (drug effects)
• Neovascularization, Pathologic (drug therapy, metabolism)
• Proanthocyanidins (pharmacology)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (metabolism)
• Veratrum Alkaloids (pharmacology)