Abstract

Human serum paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated enzyme, secreted by the liver and transported into the blood. The PON-1 can protect LDLs from oxidative stress and prevent atherosclerosis formation. GP, a folk herbal medicine in Taiwan, has antioxidative and anti-inflammatory effects. Previously, the microarray analysis was performed to examine the gene expression profiling, we found that GP could upregulate PON-1 expression in DMN-induced liver fibrotic animals. To address the effect and the molecular mechanisms of GP on PON-1 expression, human hepatoma HepG2 cells were treated with water soluble extract of GP (GP-WSE) for indicated time points. The results showed that GP-WSE could increase the level of secreted PON-1 protein and its enzymatic activity. Data from electrophoretic mobility shift assay demonstrated that the DNA binding activity of NF-kB was enhanced by GP-WSE. The NF-kB inhibitors, PDTC and BAY 11-7082, significantly reduced GP-WSE-induced PON-1 secretion and NF-kB DNA binding activity. Taken together, our observations demonstrated that GP-WSE-mediated PON-1 gene up-regulation might be via a NF-kB-dependent signaling pathway.

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