Over the last three decades, green tea has been studied for its beneficial effects, including anti-cancer, anti-obesity, anti-diabetes, anti-inflammatory, and neuroprotective effects. At present, a number of studies that have employed animal, human and cell cultures support the potential neuroprotective effects of green tea catechins against neurological disorders. However, the concentration of (−)-epigallocatechin gallate (EGCG) in systemic circulation is very low and EGCG disappears within several hours. EGCG undergoes microbial degradation in the small intestine and later in the large intestine, resulting in the formation of various microbial ring-fission metabolites which are detectable in the plasma and urine as free and conjugated forms. Recently, in vitro experiments suggested that EGCG and its metabolites could reach the brain parenchyma through the blood–brain barrier and induce neuritogenesis. These results suggest that metabolites of EGCG may play an important role, alongside the beneficial activities of EGCG, in reducing neurodegenerative diseases. In this review, we discuss the function of EGCG and its microbial ring-fission metabolites in the brain in suppressing brain dysfunction. Other possible actions of EGCG metabolites will also be discussed.

The consumption of green tea catechins (GTCs) suppresses age-related cognitive dysfunction in mice. GTCs are composed of several catechins, of which epigallocatechin gallate (EGCG) is the most abundant, followed by epigallocatechin (EGC). Orally ingested EGCG is hydrolyzed by intestinal biota to EGC and gallic acid (GA). To understand the mechanism of action of GTCs on the brain, their permeability of the blood brain barrier (BBB) as well as their effects on cognitive function in mice and on nerve cell proliferation in vitro were examined. The BBB permeability of EGCG, EGC and GA was examined using a BBB model kit. SAMP10, a mouse model of brain senescence, was used to test cognitive function in vivo. Human neuroblastoma SH-SY5Y cells were used to test nerve cell proliferation and differentiation. The in vitro BBB permeability (%, in 30 min) of EGCG, EGC and GA was 2.8±0.1, 3.4±0.3 and 6.5±0.6, respectively. The permeability of EGCG into the BBB indicates that EGCG reached the brain parenchyma even at a very low concentration. The learning ability of SAMP10 mice that ingested EGCG (20 mg/kg) was significantly higher than of mice that ingested EGC or GA. However, combined ingestion of EGC and GA showed a significant improvement comparable to EGCG. SH-SY5Y cell growth was significantly enhanced by 0.05 µM EGCG, but this effect was reduced at higher concentrations. The effect of EGC and GA was lower than that of EGCG at 0.05 µM. Co-administration of EGC and GA increased neurite length more than EGC or GA alone. Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.

Epidemiological studies have demonstrated that the intake of green tea is effective in reducing the risk of dementia. The most important component of green tea is epigallocatechin gallate (EGCG). Both EGCG and epigallocatechin (EGC) have been suggested to cross the blood–brain barrier to reach the brain parenchyma, but EGCG has been found to be more effective than EGC in promoting neuronal differentiation. It has also been suggested that the products of EGCG decomposition by the intestinal microbiota promote the differentiation of nerve cells and that both EGCG and its degradation products act on nerve cells with a time lag. On the other hand, the free amino acids theanine and arginine contained in green tea have stress-reducing effects. While long-term stress accelerates the aging of the brain, theanine and arginine suppress the aging of the brain due to their anti-stress effect. Since this effect is counteracted by EGCG and caffeine, the ratios between these green tea components are important for the anti-stress action. In this review, we describe how green tea suppresses brain aging, through the activation of nerve cells by both EGCG and its degradation products, and the reductions in stress achieved by theanine and arginine.