In previous metabolomic research on tea, almost all analyses focused on differences among production regions, and little was known about biochemical differences among cultivars. Considering this fact and our findings , functional studies on various green tea cultivars may expand the nutraceutical potential of green tea. At present, human studies suggest that consumption of green tea can reduce the risk of cardiovascular diseases such as atherosclerosis. However, the mechanisms underlying this, including direct involvement in MRLC phosphorylation, and the differences in bioactivity among various green tea cultivars remain unclear. Endothelial Z-VAD-FMK dysfunction is an early step in the development of atherosclerosis, and is associated with cardiovascular risk factors. Enhancement of MRLC phosphorylation increases contraction and permeability of ECs, and therefore promotes dysfunction of the endothelial barrier during atherogenesis. Here, we showed for the first time the ability of numerous green tea cultivars to inhibit MRLC phosphorylation in HUVECs. Although further animal and human studies are required, these results suggest that intake of green tea may help to prevent cardiovascular diseases such as atherosclerosis via a novel therapeutic target, i.e., the inhibition of MRLC phosphorylation. A combination of certain SR-specific polyphenols with an extract from the non-bioactive cultivar YB inhibited MRLC phosphorylation. The fact that certain constituents identified by SCH772984 metabolic profiling can change non-bioactive extracts into active ones suggests that this approach could be used to expand the function and utilization of some tea cultivars. To further elucidate this bioactivity-inducing mechanism, we are now investigating various combinations of single tea constituents to clarify the molecular mechanism underlying the bioactivity of SR. In the field of nutraceutical research, there are many reports on screening of plants and foods for positive bioactivity. However, there is little information about negative bioactive regulators. In addition to positive regulators in bioactive plants and foods, elucidation of negative regulators and the unique concomitant factors would be useful for the design of nutraceutical products for use in effective and safe functional foods. In that sense, combining metabolic profiling methods with bioassays can yield information on both positive and negative bioactive compounds as mentioned above.