title: Ethanol extract of Graptopetalum paraguayense upregulates paraoxonase 1 gene expression via an AKT/NF-κB-dependent pathway.
abstract: Human serum paraoxonase 1 (PON1), a calcium-dependent ester hydrolase, protects against the oxidative modification of low-density lipoprotein (LDL) and is a major anti-atherosclerotic component of high-density lipoprotein (HDL). Graptopetalum paraguayense, a folk herbal medicine commonly used in Taiwan, has antioxidative, anti-inflammatory, anti-hypertensive, and anti-atherogenic properties. The effects of G. paraguayense on the activity and/or expression of PON1 were examined using various extracts of the plant; extracts were made in water (GPWE), 50% ethanol (GP50E), and 95% ethanol (GP95E). Of these extracts, GP50E was found to be the most effective at increasing the function and expression of PON1 in a human hepatoma HepG2 cell line. Data from electrophoretic mobility shift assays and promoter-reporter luciferase analyses demonstrated that the DNA binding activity and transactivation ability of NF-κB were enhanced by GP50E. Treatment with NF-κB inhibitors, pyrrolidine dithiocarbamate, and BAY 11-7082 significantly attenuated GP50E-induced PON1 production and NF-κB transactivation activity. In addition, GP50E increased the levels of phosphorylated protein kinase B (PKB/AKT). Pharmacological inhibition of AKT by LY294002 effectively suppressed NF-κB activation and PON1 gene expression, suggesting that AKT was an upstream regulator of GP50E-mediated biological events. Overall, the results show that GP50E up-regulated PON1 gene expression via an AKT/NF-κB-dependent signaling pathway in human hepatoma HepG2 cells. This observation led to the conclusion that the anti-atherogenic characteristics of G. paraguayense are modulated, at least in part, via the up-regulation of hepatocyte PON1 gene expression.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chi-Chih
authors.initials: CC
authors.lastname: Cheng
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Wu
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Lai
authors.forename: Chen-Ting
authors.initials: CT
authors.lastname: Chen
authors.forename: Chi-Mei
authors.initials: CM
authors.lastname: Hsueh
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D029627:Crassulaceae / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D043303:Aryldialkylphosphatase