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Abstract Title:

Induction of Nrf2-mediated gene expression by dietary phytochemical flavones Apigenin and Luteolin.

Abstract Source:

Biopharm Drug Dispos. 2015 Apr 22. Epub 2015 Apr 22. PMID: 25904312

Abstract Author(s):

Ximena Paredes-Gonzalez, Francisco Fuentes, Sundrina Jeffery, Constance Lay-Lay Saw, Limin Shu, Zheng-Yuan Su, Ah-Ng Tony Kong

Article Affiliation:

Ximena Paredes-Gonzalez

Abstract:

Apigenin (API) and Luteolin (LUT) have been used as therapeutic agents in folk medicine for thousands of years. These compounds exert a variety of biological activities, including anti-cancer, anti-oxidant, and anti-inflammatory activities. In this study, we investigated whether API and LUT could activate Nrf2-antioxidant response element (ARE)-mediated gene expression and induce anti-inflammatory activities in human hepatoma HepG2 cells. The compounds did not exhibit any substantial toxicity at low doses (1.56-6.25 μM). We assessed the induction of ARE activity in HepG2-C8 cells after treatment with low doses of API and LUT for 6 and 12 h. We found that the induction of ARE activity by these compounds at the higher doses was comparable to the effects of the positive control, SFN at a dose of 6.25 μM.Exposure to the PI3K inhibitor LY294002 abolished ARE activation by both API and LUT, whereas the ERK-1/2 inhibitor PD98059 only decreased ARE activity induced by API. Both compounds significantly increased the endogenous mRNA and protein levels of Nrf2 and Nrf2 target genes with important effects on heme oxygenase-1 (HO-1) expression. API and LUT significantly and dose-dependently decreased the production of nitric oxide (NO), nitric oxide synthase (iNOS), and cytosolic phospholipase A2 (cPLA2), which were induced by the treatment of HepG2 cells with 1 µg/ml of lipopolysaccharide (LPS) for24 h. Our results indicate that API and LUT significantly activate the PI3K/Nrf2/ARE system, and this activation may be responsible for their anti-inflammatory effects, as demonstrated by the suppression of LPS-induced NO, iNOS, and cPLA2. This article is protected by copyright. All rights reserved.

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Sayer Ji
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