Induction of hepatic apolipoprotein A-I gene expression by the isoflavones quercetin and isoquercetrin.

Michael J Haas, Luisa M Onstead-Haas, Anna Szafran-Swietlik, Hagop Kojanian, Tim Davis, Paul Armstrong, Norman C W Wong, Arshag D Mooradian

Index: Life Sci. 110(1) , 8-14, (2014)

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Abstract

Phytochemicals such as flavonoids, vitamins, and polyphenols have been shown to have beneficial effects in metabolic disease. To determine if select flavonoids regulate hepatic apolipoprotein A-I (apo A-I) and high-density lipoprotein (HDL) synthesis, we examined the effects of quercetin, isoquercetin, and myrescetin on apo A-I gene expression in HepG2 (hepatocytes) and Caco-2 (intestinal) cells.Apo A-I gene expression was measured by Western blotting, quantitative reverse-transcription polymerase chain reaction, and transient transfection. Estrogen receptor α (ESR1) and estrogen receptor β expression were measured by Western blotting, and ESR1 expression was inhibited using ESR1-specific short inhibitory RNA (siRNA).Quercetin and isoquercetin, but not myrecetin, induced apo A-I protein and mRNA synthesis, and induced apo A-I promoter activity. Induction by quercetin required an estrogen-responsive region of the apo A-I promoter. Addition of estrogen receptor blocker ICI-182780 to quercetin-treated cells inhibited the effects of quercetin on apo A-I gene expression. Down-regulation of ESR1 with ESR1 siRNA had no effect on basal apo A-I gene expression; however it prevented quercetin-mediated induction of apo A-I gene expression.We conclude that quercetin induces apo A-I gene expression at least in part through induction of ESR1 and may be useful in treating hypoalphalipoproteinemia.Copyright © 2014. Published by Elsevier Inc.