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Apoptotic effect of propyl gallate in activated rat hepatic stellate cells
Authors:Xian-Hua Che  Wen-Yi Jiang  Daya Ram Parajuli  Yu-Zhe Zhao  Sung Hee Lee  Dong Hwan Sohn
Affiliation:1. Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 570-749, Korea
Abstract:Hepatic stellate cells (HSCs) play a central role in liver fibrosis. Inhibition of HSC growth and induction of apoptosis have been proposed as therapeutic strategies for the treatment and prevention of liver fibrosis. Propyl gallate (PG) is an antioxidant widely used in processed foods, cosmetics and medicinal preparations. However, the anti-fibrotic effect of PG in liver injury is unclear. In this study, we investigated whether PG could induce apoptosis in activated HSCs. Treatment of activated HSCs with PG inhibited cell viability in a dose- and time-dependent manner. PG induced apoptosis as demonstrated by morphological changes, poly(ADP-ribose) polymerase (PARP) cleavage, caspase-3 cleavage, increased Bad expression, and decreased Bcl-2 protein expression. Through stimulation of the activation of c-Jun NH2-terminal protein kinase (JNK) and p38 mitogen-activated protein kinases (MAPK) by PG treatment, we demonstrated that JNK and p38 MPAK are not involved in PG-induced apoptosis using their specific inhibitors. Taken together, these findings indicate that PG induces apoptosis in activated HSCs. The potential anti-fibrotic effect of PG warrants further evaluation.
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