Metabolism and bioactivity of catechins

Ph. D. ThesisGreen tea is widely consumed worldwide, second only to water. Its health effects have been attributed to its polyphenolic catechin content, which accounts for a significant percentage of its dry weight. Epidemiological studies have observed beneficial health effects of green tea catechins against some cancers, cardiovascular diseases, and neurodegenerative diseases. However most studies have also been carried out in vitro where the concentrations of catechins used are not obtainable in the human body. The in vivo situation is very complicated and relies on favourable absorption, metabolism, and excretion of the catechins. In this thesis it is reported, the potential health benefits of green tea catechins in tissues which are highly and most often in contact with catechins, the oral cavity and the intestine. In experiments modelling the oral cavity the four major catechins were extensively absorbed into H400 cells, and showed significant protection at physiological concentrations against H2O2 induced mitochondrial DNA damage. Thereafter the in vitro metabolism of catechins were measured using various intestinal and liver enzyme fractions. It was shown, that in these systems, glucuronidation was the main metabolism pathway. These enzyme fractions also provided mixtures of metabolites which were used to measure their comparative bioactivities in relation to their parent compounds. This was done via the assessment of their protective effects against H2O2 induced mtDNA damage in human intestinal cells. The metabolites were shown to be significantly bioactive; however the majority of the metabolites had lower bioactivities than the parent compound. In the final study the aim was to inhibit the glucuronidation of catechins to aid in the development of strategies to enhance catechin bioavailability. The two compounds chosen have previously been shown to inhibit intestinal glucuronidation. In this study it was determined that both piperine and quercetin significantly inhibited the metabolism of the catechins in intestinal microsomes. These studies taken together give a platform for future studies to be carried out which will be more detailed and rigorous.Unilever and the BBSR