The study, published in the Journal of Agricultural and Food Chemistry, investigated the structure and activity of 19 citrus flavonoids, finding that differences in the number of methoxy groups (CH3O-) in the chemical structure of the flavonoids has important effects on the compounds activity. The presence of methoxy chemical groups in the aromatic-rings changes the chemistry of the compound and, in this case, indicates that methoxylated flavonoids are more potent in reducing LDL cholesterol.
“The structure-activity analysis indicated that a fully methoxylated aromatic-ring of the flavonoid structure was associated with a potent inhibitory activity on hepatic apoB secretion,” said the authors, led by Yuguang Lin from Unilever R&D Vlaardingen.
“Tangeretin and nobiletin, which have the most optimal molecule structure, may lower blood cholesterol and triglyceride concentrations, whereas other citrus flavonoids without a fully methoxylated aromatic-ring may have virtually no or only weak lipid-lowering effects in humans,” they added.
Flavonoid benefits
Flavonoids are a group of polyphenol plant metabolites that have generated considerable interest in recent years due to their association between dietary consumption and health benefits.
The compounds have been suggested to have many healthy benefits, the evidence for which has come mainly from studies of their in vitro activity as antioxidant and anti-inflammatory agent, in addition to some in vivo animal studies.
According to Business Insights, the market for flavonoids in the dietetic and nutritional supplement market was in excess of €670m ($862m) for 2007.
Citrus flavonoids
The Unilever scientists agreed that interest in citrus flavonoids “has increased in recent years because of accumulating evidence suggesting that they may lower blood cholesterol and triglycerides” – as demonstrated in a number of previous animal studies.
However, they noted that data from human studies concerning the lipid-lowering effect of citrus flavonoids are conflicting.
“The reasons for these conflicting data are unclear … Possibly differences in the activity of the various citrus flavonoids tested in these human studies may at least partly explain the discrepancy in study outcomes,” said the authors.
So far, the underlying mechanisms of action for a lipid-lowering effect of citrus flavonoids have not yet been fully established.
The new study investigated the effect of individual citrus flavonoids and polymethoxylated flavonoids on lipid metabolism in the liver, in order to identify a structure-activity relationship among 19 citrus flavanoids.
Structural benefit
Lin and colleagues said that the study’s results indicate that full methoxylation of the aromatic-ring of citrus flavonoids “appears to be the most optimal structure” to have potent effects on adjusting liver lipid metabolism primarily by suppressing apoB-containing lipoprotein secretion (Apolipoprotein B (ApoB) is the primary lipid transport protein (apolipoprotein) for low-density lipoproteins (LDL), and high levels are related to heart disease)
The researchers reported that polymethoxylated citrus flavonoids such as tangeretin and nobiletin, “potently inhibited apoB secretion and modestly reduced cholesterol and triglyceride synthesis.”
However they found that non-polymethoxylated flavonoids (such as hesperetin and naringenin) had only weak effects on cholesterol and triglyceride syntheses and apoB secretion.
Source: Journal of Agricultural and Food Chemistry
Published online ahead of print, doi: 10.1021/jf1044475
“Molecular Structures of Citrus Flavonoids Determine Their Effects on Lipid Metabolism in HepG2 Cells by Primarily Suppressing ApoB Secretion”
Authors: Y. Lin, M.A. Vermeer, W. Bos, L. van Buren, E. Schuurbiers, S. Miret-Catalan, E.A. Trautwei