Tea flavonoids: bioavailability in vivo and effects on cell signaling pathways in vitro

The elucidation of the potential health benefits of tea beverage continues to be a focus of research in many laboratories. Beneficial effects of tea have been particularly evident in animal tumorigenesis models, with green and black tea frequently demonstrating similar effectivity. Human data are now emerging to support a beneficial role for tea in cardiovascular disease, but the data with respect to cancer risk at various sites remain inconclusive. The constituent flavonoids of green and black tea beverage are known to be potent antioxidants, and although this may be a major factor in explaining their biological activity, it appears that the gallated flavonoids in particular (e.g., epigallocatechin gallate and the gallated theaflavins) impact on a wide range of molecular targets that influence cell growth and more specifically pathways such as those involving angiogenesis. Data on the pharmacokinetic properties of tea flavonoids, primarily on the catechins and therefore related most closely to green tea, have provided indications of the plasma levels and circulating molecular forms that may be expected in humans following tea consumption. The structural complexity of black tea flavonoids, in particular the thearubigins, has hindered efforts to describe their bioavailability and to perform mechanistic studies. Recent studies on the effects of catechins and theaflavins on growth factor-, nuclear factor-kappaB-, and stress-mediated signal transductions are described in this review, where possible in relation to their bioavailability in vivo. These studies indicate that effects that may be relevant to both cancer and atherosclerosis are often observed at tea flavonoid levels that could realistically be encountered in vivo. However, more studies need to be performed using those molecular forms of tea flavonoids (methylated, sulfated, and glucuronidated conjugates) that are the major circulating species encountered following tea consumption. Such studies, combined with further human epidemiological and interventional data, should ultimately elucidate the full beneficial potential of tea beverage on human health.