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

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.