Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 2/20/2001
Publication Date: 3/1/2002
Citation: Kurowska, E.M., Manthey, J.A. Regulation of lipoprotein metabolism in HepG2 cells by citrus flavonoids. Buslig, B.S., Manghey, J.A., editors. Kluwer Academic/Plenum Publishers, New York, NY. Flavonoids in Cell Function. 2002. p. 173-180. Interpretive Summary: Elevated levels of cholesterol is a primary risk factor for the development of heart disease. Cholesterol levels can be controlled to a certain extent by diet, and correlations have been made between the consumption of high levels of fruits and vegetables and decreased risk of heart disease. The contributions of plants to decreased risk levels for heart disease are due to beneficial plant compounds such as the flavonoids. The present study shows that certain flavonoids in citrus juices are able to inhibit important steps in cholesterol release by human liver cells, which is a main control point dictating blood cholesterol levels. This evidence suggests that the citrus flavonoids are active agents contributing to the cholesterol-lowering and other cardioprotective effects of citrus juice consumption observed in a number of different animal studies.
Technical Abstract: Elevated levels of blood cholesterol are known to be one of the major risk factors associated with coronary heart disease. Epidemiological studies have shown that diets rich in fruits and vegetables are associated with reduced risk of heart disease, and plant flavonoids may significantly contribute to these protective effects. Using a rabbit model of hypercholesterolemia, consumption of citrus juices was shown to significantly lower low-density lipoprotein (LDL) cholesterol levels. In human subjects, citrus juice consumption was associated with a rise in the levels of beneficial high-density lipoprotein, but no change occurred in LDL. Individual flavonoid components of citrus were shown to suppress the release of the apoprotein B, the structural protein component of LDL, by cultured human liver cells. Several classes of flavonoids were investigated, including flavanone aglycones, glycosides and, polymethoxylated flavone aglycones. These latter species were shown to be particularly active inhibitors. Synthetic PMF analogs were also analyzed, but were shown to be less active than the naturally-occurring compounds. The strong inhibitory actions of the PMFs in citrus suggest that they may be useful cardioprotective agents in humans.