Microarray and pathway analysis highlight Nrf2/ARE‐mediated expression profiling by polyphenolic myricetin

Abstract

Myricetin is a dietary flavonol and widely distributed in many edible plants. It has been reported to have many bioactivities and considered as a promising chemopreventive compound. The present study aimed to investigate the influences of myricetin on gene expressions in genome-wide and underlying mechanisms. Among total 44K gene probes, myricetin treatment upregulated the signals of 143 gene probes (0.33% of total probes) and downregulated signals of 476 gene probes (1.08% of total probes) by greater than or equal to twofold in HepG2 cells. The network pathway analysis revealed that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response element (ARE) activation is involved in myricetin-induced genes expressions. Molecular data revealed that myricetin activated Nrf2-ARE pathway by inhibiting Nrf2 ubiquitination and protein turnover, stimulating Nrf2 expression and kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 modification. All of these events finally increased nuclear Nrf2 accumulation and ARE-binding activity to enhance ARE-mediated genes expressions. Additionally, treatment with Nrf2 small interfering RNA attenuated the myricetin-induced ARE activity and gene expression. An Nrf2-mediated ARE activation is involved in myricetin-induced expression profiling in hepatic cells.