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標題: Ethanol Extract of Graptopetalum paraguayense Upregulates Paraoxonase 1 Gene Expression via an AKT/NF-kappa B-Dependent Pathway
作者: Cheng, C.C.
Wu, L.C.
Lai, J.M.
Chen, C.T.
Hsueh, C.M.
Hsu, S.L.
關鍵字: Paraoxonase 1;Graptopetalum paraguayense;NF-kappa B;AKT;Hepatoma;Cell Line;necrosis-factor-alpha;serum paraoxonase;diabetes-mellitus;protein-kinase;walther,e. extracts;hepg2 cells;lipoproteins;activation;induction;atherosclerosis
Project: American Journal of Chinese Medicine
期刊/報告no:: American Journal of Chinese Medicine, Volume 40, Issue 2, Page(s) 357-372.
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, antihypertensive, 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-kappa B were enhanced by GP50E. Treatment with NF-kappa B inhibitors, pyrrolidine dithiocarbamate, and BAY 11-7082 significantly attenuated GP50E-induced PON1 production and NF-kappa B transactivation activity. In addition, GP50E increased the levels of phosphorylated protein kinase B (PKB/AKT). Pharmacological inhibition of AKT by LY294002 effectively suppressed NF-kappa B 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 kappa B-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.
ISSN: 0192-415X
DOI: 10.1142/s0192415x12500280
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