Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet-derived growth factor-induced proliferation of the human hepatic stellate cell line LI90.
OBJECTIVE
Hepatic stellate cell (HSC) proliferation plays a pivotal role in liver fibrogenesis, and agents that suppress HSC activation, including platelet-derived growth factor (PDGF)-induced HSC proliferation, are good candidates for antifibrogenic therapies. In this report, we use the LI90 HSC line to elucidate the antifibrogenic effects of proanthocyanidin derived from the leaves of Vaccinium virgatum.


METHODS
Proanthocyanidin (PAC) was extracted from the leaves of blueberry V. virgatum (BB-PAC), grape seeds (GS-PAC) and Croton lechleri (CL-PAC). These extracts were examined for their effects on PDGF-BB-induced LI90 cell proliferation and DNA synthesis. Extracellular signal-regulated kinase (ERK) and Akt phosphorylation and PDGF receptor-beta (PDGFR-beta) expression were evaluated by western blot analysis.


RESULTS
BB-PAC potently suppressed PDGF-BB-induced proliferation and DNA synthesis of LI90 cells. BB-PAC also suppressed PDGF-BB-induced DNA synthesis in primary cultured rat HSC. Moreover, GS-PAC and CL-PAC suppressed PDGF-BB-induced DNA synthesis in LI90 cells. In contrast, the monomeric PAC catechin and epicatechin and dimeric PAC procyanidin B2 only slightly suppressed PDGF-BB-induced DNA synthesis. Western blot analysis showed that BB-PAC completely or partially inhibited PDGF-BB-induced ERK and Akt phosphorylation, respectively. In addition, BB-PAC partially inhibited the PDGF-BB-induced degradation of PDGFR-beta.


CONCLUSIONS
Our results suggest that BB-PAC suppresses activated HSC by inhibiting the PDGF signaling pathway. In addition, these results provide novel findings that may facilitate the development of antifibrogenic agents.
Takami
Yoichiro
Y
Digestive Disease and Lifestyle-Related Disease Health Research, Human and Environmental Sciences, Kagoshima University Graduate School of Medicine and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Uto
Hirofumi
H
Takeshita
Masahiko
M
Kai
Hisahiro
H
Akamatsu
Ena
E
Moriuchi
Akihiro
A
Hasegawa
Susumu
S
Oketani
Makoto
M
Ido
Akio
A
Kataoka
Hiroaki
H
Tsubouchi
Hirohito
H