“UGT1A1 Induction by Chrysin in Primary Human Hepatocytes and HEPG2 Cells,” by Cornelia M. Smith and Edward L. LeCluyse, Drug Metabolism Reviews, 35, Supplement 2, 2003, p. 122.
The correct version of the abstract is as follows:
Chrysin, a dietary flavonoid, has been shown to induce markedly UGT1A1 expression in HepG2 and Caco‐2 cell lines. Primary human hepatocytes were used to further characterize the effects of Chrysin on UGT1A1 regulation. Additionally, transient co‐transfection reporter assays were conducted in HepG2 cells using a 290‐bp region of the UGT1A1 promoter (gtPBREM) in the presence or absence of the nuclear receptor, CAR. UGT1A1 immunoreactive protein and activity were evaluated by densitometric analyses of immunoblots and using 7‐ethoxycoumarin as probe substrate, respectively. Cultured hepatocytes were treated with 0.1% DMSO, 5 µM 3‐methylcholanthrene (3‐MC), and 25 µM Chrysin. HepG2 cells were treated with 0.1% DMSO and varying concentrations of Chrysin. UGT1A1 protein was moderately induced in primary hepatocytes by Chrysin (1.4‐fold) when compared to induction by 3‐MC (2.2‐fold). UGT catalytic activities were not induced by Chrysin, but exhibited a 3.6‐fold increase after 3‐MC treatment in primary hepatocytes. A concentration‐response profile of gtPBREM activation by Chrysin generated an EC50 of 3.6 µM and Emax at 10 µM. At the optimal concentration of 10 µM, reporter activities were induced 3.7‐fold with the gtPBREM construct alone and induced 3.9‐fold when co‐transfected with CAR. These results indicate that other processes operative in the primary cells may significantly limit the overall impact of Chrysin on UGT regulation. Moreover, induction of UGT1A1 by Chrysin is mediated through the gtPBREM response element.