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- Title
Ethanol Extract of Graptopetalum paraguayense Upregulates Paraoxonase 1 Gene Expression via an AKT/NF-κB-Dependent Pathway.
- Authors
Cheng, Chi-Chih; Wu, Li-Chen; Lai, Jin-Mei; Chen, Chen-Ting; Hsueh, Chi-Mei; Hsu, Shih-Lan
- 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.
- Subjects
HERBAL medicine; ATHEROSCLEROSIS; ELECTROPHORESIS; ESTERASES; GENE expression; HEPATOCELLULAR carcinoma; CHINESE medicine; OXIDOREDUCTASES; POLYMERASE chain reaction; RESEARCH funding; T-test (Statistics); WESTERN immunoblotting; PLANT extracts; DATA analysis software; DESCRIPTIVE statistics
- Publication
American Journal of Chinese Medicine, 2012, Vol 40, Issue 2, p357
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X12500280