Black tea is, second only to water, the most consumed beverage globally with an average per capita consumption of around 550 ml per day. The annual production of tea leaves reached a record high in 2008 with a global harvest of 3.75. Mt . Production of dried tea comprises 20% green, 2% oolong and the remainder black. Following black tea, coffee is the third most consumed beverage globally with an annual production of 9.7 Mt and a daily consumption of around 300 ml (data from http://www.fas.usda.gov/, obtained 1st March 2011). Strong epidemiological evidence has repeatedly linked the consumption both black tea  and coffee [3, 4] to a variety of beneficial health effects, among them is the prevention of multifactorial diseases including cancer, cardiovascular disease and neurological disorders as well as a series of psychoactive responses improving alertness, mood and general mental performance [5–8]. Recently, Unilever made an application for a health claim, in which the black tea beverage should supposedly improve mental alertness and focus, based on studies by Nurk et al. with the activities of the two compounds caffeine and L-theanine as the proposed rationale . While epidemiological studies link two causally unrelated events, e. g. a beneficial health effect with the consumption of a certain diet, with a certain statistical probability, the molecular causes of these epidemiological observations are rarely known. In order to rationalize epidemiological observations, a biological target must be identified that is mechanistically linked to the beneficial health effect reported, as well as the specific molecules contained in the diet that interact with the biological target in question at dietary and physiologically relevant concentrations. The search for such matching pairs of biological targets and dietary compound must be considered an exercise of fishing in the dark, however, where enzymes known to be intimately involved in the area in question need to be systematically screened against secondary metabolites known to be produced by the dietary plant in question.
Prompted by reports of Fang and co-workers, who have recently reported the inhibition of DNA methyltransferase 1 (Dnmt1) by a series of dietary polyphenols  and work by Lee and co-workers on the inhibition of the same enzyme investigating most notably epi-gallocatechin gallate (EGCG)  (the main polyphenolic constituent of green tea) and 5-caffeoyl quinic acid  (the main phenolic constituent of the green coffee bean), and Nandakumar, showing the reduction of cellular DNA methylation after admission of (-)-epigallocatechin-3-gallate , we decided to screen the interaction of a series of black tea and coffee polyphenols against DNA methyltransferase 3a, another important member of this family of enzymes.
DNA methyltransferases catalyzes methylation of DNA at cytosine residues and play an important role in epigenetic regulation of gene expression, X-chromosome inactivation, genomic imprinting, and development cellular aging and cell differentiation [14, 15]. In mammals, DNA methylation is catalyzed mainly by three DNA methyltransferases [15, 16]: Dnmt1, Dnmt3a, and Dnmt3b. Dnmt1 has a high preference for hemimethylated DNA and is essential for maintaining the methylation patterns during each round of DNA replication. On the other hand, Dnmt3a and Dnmt3b modify both unmethylated and hemimethylated DNA and are responsible for de novo methylation during early development. Errors in DNA methylation contribute to both the initiation and the progression of various cancers [17, 18]. In addition, aberrant or missing DNA methylation causes many kinds of diseases which include defects in embryonic development or brain development and neurological defects which are also associated with behavioral changes . Hypermethylation of genes is one of important process in cancer development, typically resulting in the repression of tumor suppressor genes. Preventing the hypermethylation of promoter genes by selective inhibition of methyltransferases could pave a way for cancer treatment [20–22]. Importantly it has been shown that upon use of methyltransferase inhibitors it was possible to reactivate gene silenced by promoter methylation in cancers and thus modulate gene expression. Several efforts are directed at developing small molecules that target DNA methyltransferases and other elements of the machinery, as the proteins that bind to methylated CpG; some are in clinical trials [20–22].
Another important issue of DNA methylation is its function in brain development. Levenson and coworkers showed that Dnmt1 is involved in the formation of hippocampus-dependent long term memory . They found that the promoters for reelin and brain-derived neurotrophic factor (genes implicated in the induction of synaptic plasticity in the adult hippocampus) exhibit rapid and dramatic changes in cytosine methylation when Dnmt1 activity was inhibited. Moreover, DNA methyltransferase inhibitors like 5-aza-2-deoxycytidine blocked the induction of long term potentiation at Schaffer collateral synapses. Furthermore, Dnmt3a-dependent DNA methylation has been reported to influence transcription of neurogenic genes . Additional studies showed that Dnmt1 and Dnmt3a regulate synaptic function in adult forebrain neurons  and Dnmt3a affects plasticity of neurons .
Changes in the DNA methylation pattern of regions in the hippocampus are associated with behavioral changes in rat . In addition, Dnmt3a has been recently shown to affect the emotional behaviour . Thus, DNA methylation which is already known to be involved in setting up cellular memory is also involved in brain function. The combination of studies in cell lines and in animal models, coupled with data obtained from post-mortem human material provides compelling evidence that aberrant methylation may contribute to psychiatric diseases like schizophrenia and psychosis . Strong epidemiological evidence suggests that particularly for black tea and green tea there is an inverse relation between intake and significant beneficial effects on patients suffering from psychological disorders [2, 5–8]. Currently, no accepted rationale on the molecular level exists that can account for these epidemiological findings. Dnmts are a possible biological target for tea dietary polyphenols suggesting a molecular based rationale for the observed biological activities.