Oral flavonoid supplementation attenuates atherosclerosis development in apolipoprotein E-deficient mice.

OBJECTIVE Caffeic acid phenethyl ester (CAPE), a natural flavonoid, specifically blocks activation of nuclear factor-kappaB (NF-kappaB). We examined the effects of oral CAPE supplementation on atherogenesis in apolipoprotein E-deficient (apoE-/-) mice. METHODS AND RESULTS Ten-week-old male apoE-/- mice were supplemented orally with CAPE (30 mg/kg body weight) for 12 weeks. At the end of administration, atherosclerosis progression, NF-kappaB activity, gene expression profiling by microarray analysis, and oxidative stress were studied. Treatment of apoE-/- mice with CAPE significantly reduced aortic atherosclerosis, NF-kappaB activity, and expression of NF-kappaB-related genes in the aorta. Moreover, expression of other gene clusters such as basic transcription factors, growth factors, cytokines, cell adhesion proteins, and extracellular matrix were also significantly reduced by treatment with CAPE. Plasma isoprostane level in apoE-/- mice was also significantly reduced by CAPE. CONCLUSIONS In apoE-/- mice, oral CAPE supplementation attenuates the atherosclerotic process. This may be attributable to direct inhibition of NF-kappaB in the lesion and reduction of systemic oxidative stress. In apoE-/- mice, oral caffeic acid phenethyl ester (CAPE) supplementation attenuates the atherosclerotic process and reduces NF-kappaB activity and expression of NF-kappaB-related genes in the aorta. This may be attributable to direct inhibition of NF-kappaB in the lesion and reduction of systemic oxidative stress.