Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits

The anti-atherogenic effects of the citrus flavonoids, naringin and naringe nin, were evaluated in high cholesterol-fed rabbits. At 3 months of age, 30 male New Zealand White (NZW) rabbits were divided into three groups (n = 1 0 per group). The rabbits were fed a 1% cholesterol diet alone (control gro up) or a diet supplemented with either 0.1% naringin or 0.05% naringenin fo r 8 weeks. The plasma lipoprotein levels, total cholesterol, triglyceride, and high-density lipoprotein showed no significant differences in the contr ol and experimental groups. Hepatic acyl-CoA: cholesterol acyltransferase ( ACAT) activity was slightly low in naringin (5.0%)- and naringenin (15.0%)- fed rabbits, compared to control group. The aortic fatty streak areas were significantly lower in both the naringin (19.2 +/- 5.6%)- and naringenin (1 8.1 +/- 6.5%)-supplemented groups than in the control group (60.4 +/- 14.0% ). The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1), by semiquantitative RT-PCR analysis of the thoracic aorta, were significantly lower in the flavonoids suppleme nted groups than in the control group. These results suggest that the anti- atherogenic effect of the citrus flavonoids, naringin and naringenin, is in volved with a decreased hepatic ACAT activity and with the downregulation o f VCAM-1 and MCP-1 gene expression. (C) 2001 Academic Press.