Benzo[a]pyrene (BaP) causes
atherosclerosis by activating the
aromatic hydrocarbon receptor (AHR) signaling pathway to trigger lipid peroxidation and
inflammation, thereby promoting the development of
atherosclerosis.
Hesperidin (Hsd), one of the 60
flavonoids of citrus, exhibits
therapeutic effects on
atherosclerosis. However, its antagonistic function for BaP remains unclear. In this study, the EA.hy926 cell model was used to systematically examine the antagonistic effect of Hsd with BaP, especially in
low-density lipoprotein (
LDL) oxidation and transport. Results showed that Hsd could reduce BaP-induced AHR activation in
mRNA and
protein expression level, and reduce
LDL accumulation by decreasing the BaP-induced expression of
advanced glycation end products and enhancing the BaP-inhibited
Adenosine Triphosphate-binding cassette transporter A1 (
ABCA1) protein and
mRNA expression in EA.hy926 cells. In addition, Hsd could antagonize BaP-induced interaction of
reactive oxygen species and the subsequent generation of
oxidized LDL and
malondialdehyde. Finally, Hsd could alleviate BaP-induced inflammatory response by decreasing IL-1β and TNF-α expression. All these results suggest that Hsd suppresses
LDL accumulation, oxidation, and inflammatory response, and thus strongly impedes the AHR pathway activated by BaP.