68 : Metabolism of dietary flavonoids alters their effect on tumor necrosis factor-α

Flavonoids are polyphenolic secondary metabolites formed by many plants including fruits and vegetables, and are therefore commonly consumed in the diet. Epidemiological evidence suggests that consuming a diet high in fruits and vegetables is positively correlated with a lower incidence of cardiovascular disease (CVD). It has long been hypothesised that flavonoids are central to these beneficial effects, however the exact mechanisms of action remain unclear. Upon consumption of a parent flavonoid, degradation and metabolism occur within the body. We hypothesise that the metabolites are responsible for the health benefits as opposed to their parent compounds. Here 6 parent flavonoids, 4 B-ring degradation products and 10 conjugated flavonoid metabolites were screened for ability to reduce lipopolysaccharide-induced tumour necrosis factor- α (TNF- α ) secretion in a human monocytic cell line (THP-1). Physiologically relevant levels of treatments (0.1–10 μM) were pre-incubated in the culture model for 30 min prior to LPS stimulation. These concentrations were not cytotoxic as established using the WST-1 assay. Quercetin, epicatechin and cyanidin-3-glucoside form a common degradation product, protocatechuic acid (PCA), following ingestion. PCA can be metabolised by the liver to form glucuronide and sulfate conjugates. PCA-3-sulfate significantly decreased (38.7%, p α protein secretion compared to control. This reduction was greater than was elicited by treatment with quercetin (25.6%), epicatechin (21.3%), cyanidin-3-glucoside (13.7%) or PCA (22.1%). Furthermore, sulfation at carbon-3 gave rise to a greater reduction in TNF- α than sulfation at carbon-4 (9.6%) or by glucuronidation at either of these two sites (19.9%, 10.3% respectively). Intriguingly these protein data are not corroborated at the mRNA level, suggesting the treatments are having a post-translational effect. In conclusion, metabolism of parent flavonoids may increase their anti-inflammatory bioactivity. The possibile post-translational effects of flavonoids on TNF- α are currently the focus of our research.